Authors,Title,Year,Source title,Volume,Issue,Art. No.,Page start,Page end,Page count,Cited by,Link,Affiliations,Authors with affiliations,Abstract,Author Keywords,Index Keywords,Molecular Sequence Numbers,Chemicals/CAS,Tradenames,Manufacturers,Funding Details,References,Correspondence Address,Editors,Sponsors,Publisher,Conference name,Conference date,Conference location,Conference code,ISSN,ISBN,CODEN,DOI,PubMed ID,Language of Original Document,Abbreviated Source Title,Document Type,Source
"Lotia S., Montojo J., Dong Y., Bader G.D., Pico A.R.","Cytoscape app store",2013,"Bioinformatics",29,10,,1350,1351,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84877944199&partnerID=40&md5=89bf09cc5d48de81cb8eddae655b9eb9","Gladstone Institutes, San Francisco, CA 94158, United States; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada","Lotia, S., Gladstone Institutes, San Francisco, CA 94158, United States; Montojo, J., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Dong, Y., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Pico, A.R., Gladstone Institutes, San Francisco, CA 94158, United States","Cytoscape is an open source software tool for biological network visualization and analysis, which can be extended with independently developed apps. We launched the Cytoscape App Store to highlight the important features that apps add to Cytoscape, enable researchers to find and install apps they need and help developers promote their apps. © 2013 The Author. Published by Oxford University Press. All rights reserved.",,,,,,,,"Bindea, G., ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks (2009) Bioinformatics, 25, pp. 1091-1093; Cline, M.S., Integration of biological networks and gene expression data using Cytoscape (2007) Nat. Protoc., 2, pp. 2366-2382; Shannon, P., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res., 13, pp. 2498-24504","Pico, A.R.; Gladstone Institutes, San Francisco, CA 94158, United States; email: apico@gladstone.ucsf.edu",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/btt138,,"English","Bioinformatics",Article,Scopus
"Xin X., Gfeller D., Cheng J., Tonikian R., Sun L., Guo A., Lopez L., Pavlenco A., Akintobi A., Zhang Y., Rual J.-F., Currell B., Seshagiri S., Hao T., Yang X., Shen Y.A., Salehi-Ashtiani K., Li J., Cheng A.T., Bouamalay D., Lugari A., Hill D.E., Grimes M.L., Drubin D.G., Grant B.D., Vidal M., Boone C., Sidhu S.S., Bader G.D.","SH3 interactome conserves general function over specific form",2013,"Molecular Systems Biology",9,, 652,,,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84876580944&partnerID=40&md5=e77f23f0ed5102ca6c723f9ab976c0d9","Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, United States; Cell Signaling Technology, Danvers, MA, United States; Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA, United States; Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States; Department of Genetics, Harvard Medical School, Boston, MA, United States; Department of Molecular Biology, Genentech, South San Francisco, CA, United States; IMR Laboratory, UPR 3243, Institut de Microbiologie de la Mé Ditéranné e, Marseille Cedex 20, France; Division of Biological Sciences, Center for Structural and Functional Neuroscience, University of Montana, Missoula, MT, United States; Department of Computer Science, University of Toronto, Toronto, ON, Canada; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Swiss Institute of Bioinformatics, Molecular Modelling, Génopode, 1015 Lausanne, Switzerland; MedImmune, 24500 Clawiter Road, Hayward, CA 94541, United States; Department of Translational Sciences, Biogen Idec, Cambridge, MA 02142, United States; Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, United States; Department of Pathology, University of Michigan, Ann Arbor, MI, United States; Division of Science and Math, Center for Genomics and Systems Biology, New York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates","Xin, X., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Gfeller, D., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Swiss Institute of Bioinformatics, Molecular Modelling, Génopode, 1015 Lausanne, Switzerland; Cheng, J., Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States, MedImmune, 24500 Clawiter Road, Hayward, CA 94541, United States; Tonikian, R., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Translational Sciences, Biogen Idec, Cambridge, MA 02142, United States; Sun, L., Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, United States, Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, United States; Guo, A., Cell Signaling Technology, Danvers, MA, United States; Lopez, L., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Pavlenco, A., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Akintobi, A., Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, United States; Zhang, Y., Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA, United States; Rual, J.-F., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States, Department of Pathology, University of Michigan, Ann Arbor, MI, United States; Currell, B., Department of Molecular Biology, Genentech, South San Francisco, CA, United States; Seshagiri, S., Department of Molecular Biology, Genentech, South San Francisco, CA, United States; Hao, T., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Yang, X., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Shen, Y.A., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Salehi-Ashtiani, K., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States, Division of Science and Math, Center for Genomics and Systems Biology, New York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates; Li, J., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Cheng, A.T., Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States; Bouamalay, D., Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States; Lugari, A., IMR Laboratory, UPR 3243, Institut de Microbiologie de la Mé Ditéranné e, Marseille Cedex 20, France; Hill, D.E., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Grimes, M.L., Division of Biological Sciences, Center for Structural and Functional Neuroscience, University of Montana, Missoula, MT, United States; Drubin, D.G., Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United States; Grant, B.D., Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, United States; Vidal, M., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Boone, C., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Sidhu, S.S., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bader, G.D., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Computer Science, University of Toronto, Toronto, ON, Canada","Src homology 3 (SH3) domains bind peptides to mediate protein-protein interactions that assemble and regulate dynamic biological processes. We surveyed the repertoire of SH3 binding specificity using peptide phage display in a metazoan, the worm Caenorhabditis elegans, and discovered that it structurally mirrors that of the budding yeast Saccharomyces cerevisiae. We then mapped the worm SH3 interactome using stringent yeast two-hybrid and compared it with the equivalent map for yeast. We found that the worm SH3 interactome resembles the analogous yeast network because it is significantly enriched for proteins with roles in endocytosis. Nevertheless, orthologous SH3 domain-mediated interactions are highly rewired. Our results suggest a model of network evolution where general function of the SH3 domain network is conserved over its specific form. © 2013 EMBO and Macmillan Publishers Limited.","network evolution; phage display; protein interaction conservation; SH3 domains; yeast two-hybrid","protein SH3; amino acid sequence; article; budding; Caenorhabditis elegans; controlled study; endocytosis; gene mapping; human; human cell; nonhuman; open reading frame; phage display; priority journal; protein assembly; protein binding; protein domain; protein function; protein localization; protein motif; protein protein interaction; Saccharomyces cerevisiae; sequence homology; two hybrid system; worm",,,,,,"Akbarzadeh, S., Ji, H., Frecklington, D., Marmy-Conus, N., Mok, Y.F., Bowes, L., Devereux, L., Dorow, D.S., Mixed lineage kinase 2 interacts with clathrin and influences clathrin-coated vesicle trafficking (2002) J Biol Chem, 277, pp. 36280-36287; Anggono, V., Robinson, P.J., Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: Role in synaptic vesicle endocytosis (2007) Journal of Neurochemistry, 102 (3), pp. 931-943. , DOI 10.1111/j.1471-4159.2007.04574.x; 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Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; email: charlie.boone@utoronto.ca",,,,,,,,17444292,,,10.1038/msb.2013.9,,"English","Mol. Syst. Biol.",Article,Scopus
"Antoniotti M., Bader G.D., Caravagna G., Crippa S., Graudenzi A., Mauri G.","GeStoDifferent: A Cytoscape plugin for the generation and the identification of gene regulatory networks describing a stochastic cell differentiation process",2013,"Bioinformatics",29,4,,513,514,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84874340854&partnerID=40&md5=da78832b54934c1792880f50c78c8358","Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy; Bader Lab, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, Department of Computer Science, University of Toronto, Toronto, ON, Canada","Antoniotti, M., Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy; Bader, G.D., Bader Lab, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Department of Computer Science, University of Toronto, Toronto, ON, Canada; Caravagna, G., Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy; Crippa, S., Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy; Graudenzi, A., Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy; Mauri, G., Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy","The characterization of the complex phenomenon of cell differentiation is a key goal of both systems and computational biology. GeStoDifferent is a Cytoscape plugin aimed at the generation and the identification of gene regulatory networks (GRNs) describing an arbitrary stochastic cell differentiation process. The (dynamical) model adopted to describe general GRNs is that of noisy random Boolean networks (NRBNs), with a specific focus on their emergent dynamical behavior. GeStoDifferent explores the space of GRNs by filtering the NRBN instances inconsistent with a stochastic lineage differentiation tree representing the cell lineages that can be obtained by following the fate of a stem cell descendant. Matched networks can then be analyzed by Cytoscape network analysis algorithms or, for instance, used to define (multiscale) models of cellular dynamics.Availability: Freely available at http://bimib.disco.unimib.it/index.php/Retronet#GESTODifferent or at the Cytoscape App Store http://apps.cytoscape.org/. © 2013 The Author.",,,,,,,,"Graudenzi, A., A multiscale model of intestinal crypts dynamics (2012) Proceedings of the Italian Workshop on Artificial Life and Evolutionary Computation, , WIVACE 2012 number ISBN: 978-88-903581-2-8; Hoffman, M., Noise driven stem cell and progenitor population dynamics (2008) PLoS ONE, 3, pp. e2922; Kauffman, S., Metabolic stability and epigenesis in randomly constructed genetic nets (1969) J. Theor. Biol, 22, pp. 437-467; Smoot, M., Cytoscape 2.8: New features for data integration and network visualization (2011) Bioinformatics, 27, pp. 431-432; Villani, M., A dynamical model of genetic networks for cell differentiation (2011) PLoS ONE, 6, pp. e17703; Yamanaka, S., Elite and stochastic models for induced pluripotent stem cell generation (2009) Nature, 460, pp. 49-52","Antoniotti, M.; Department of Informatics Systems and Communication, University of Milan Bicocca, Viale Sarca 336, 20126, Milano, Italy; email: marco.antoniotti@unimib.it",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/bts726,,"English","Bioinformatics",Article,Scopus
"Reimand J., Bader G.D.","Systematic analysis of somatic mutations in phosphorylation signaling predicts novel cancer drivers",2013,"Molecular Systems Biology",9,, 637,,,,2,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84873802661&partnerID=40&md5=fcc8fd8eb80b3892d3947ff6f8c4b20f","Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada","Reimand, J., Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada; Bader, G.D., Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada","Large-scale cancer genome sequencing has uncovered thousands of gene mutations, but distinguishing tumor driver genes from functionally neutral passenger mutations is a major challenge. We analyzed 800 cancer genomes of eight types to find single-nucleotide variants (SNVs) that precisely target phosphorylation machinery, important in cancer development and drug targeting. Assuming that cancer-related biological systems involve unexpectedly frequent mutations, we used novel algorithms to identify genes with significant phosphorylation-associated SNVs (pSNVs), phospho-mutated pathways, kinase networks, drug targets, and clinically correlated signaling modules. We highlight increased survival of patients with TP53 pSNVs, hierarchically organized cancer kinase modules, a novel pSNV in EGFR, and an immune-related network of pSNVs that correlates with prolonged survival in ovarian cancer. Our findings include multiple actionable cancer gene candidates (FLNB, GRM1, POU2F1), protein complexes (HCF1, ASF1), and kinases (PRKCZ). 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Wu, L., Ma, C.A., Zhao, Y., Jain, A., Aurora B interacts with NIR-p53, leading to p53 phosphorylation in its DNA-binding domain and subsequent functional suppression (2011) J Biol Chem, 286, pp. 2236-2244; Wysocka, J., Myers, M.P., Laherty, C.D., Eisenman, R.N., Herr, W., Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 (2003) Genes Dev, 17, pp. 896-911","Reimand, J.; Donnelly Centre, University of Toronto, 160 College Street, Toronto, M5S 3E1, Canada; email: Juri.Reimand@utoronto.ca",,,,,,,,17444292,,,10.1038/msb.2012.68,,"English","Mol. Syst. Biol.",Article,Scopus
"Aebersold R., Bader G.D., Edwards A.M., Van Eyk J.E., Kussmann M., Qin J., Omenn G.S.","The biology/disease-driven human proteome project (B/D-HPP): Enabling protein research for the life sciences community",2013,"Journal of Proteome Research",12,1,,23,27,,1,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84874074018&partnerID=40&md5=41bf64e86ae2957896407e1fcb168542","Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland; Faculty of Science, University of Zurich, Zurich, Switzerland; Donnelly Centre, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, Toronto M5G 2M9, Canada; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Proteomics and Metabonomics Core, Nestlé Institute of Health Sciences, Lausanne, Switzerland; Faculty of Life Sciences, Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland; Faculty of Science, Aarhus University, Aarhus, Denmark; State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, China; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States; Departments of Computational Medicine and Bioinformatics, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2218, United States; Institute for Systems Biology, Seattle, WA 98101, United States","Aebersold, R., Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland, Faculty of Science, University of Zurich, Zurich, Switzerland; Bader, G.D., Donnelly Centre, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Edwards, A.M., Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada, Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, Toronto M5G 2M9, Canada; Van Eyk, J.E., Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States; Kussmann, M., Donnelly Centre, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, Proteomics and Metabonomics Core, Nestlé Institute of Health Sciences, Lausanne, Switzerland, Faculty of Life Sciences, Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland, Faculty of Science, Aarhus University, Aarhus, Denmark; Qin, J., State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, China, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, United States; Omenn, G.S., Departments of Computational Medicine and Bioinformatics, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2218, United States, Institute for Systems Biology, Seattle, WA 98101, United States","The biology and disease oriented branch of the Human Proteome Project (B/D-HPP) was established by the Human Proteome Organization (HUPO) with the main goal of supporting the broad application of state-of theart measurements of proteins and proteomes by life scientists studying the molecular mechanisms of biological processes and human disease. This will be accomplished through the generation of research and informational resources that will support the routine and definitive measurement of the process or disease relevant proteins. The B/D-HPP is highly complementary to the C-HPP and will provide datasets and biological characterization useful to the C-HPP teams. In this manuscript we describe the goals, the plans, and the current status of the of the B/D-HPP. © 2012 American Chemical Society.","Affinity reagents; Biological processes; Human disease; Human proteome project; Mass spectrometry; Network biology; Proteomics","biological phenomena and functions concerning the entire organism; biomedicine; human; molecular biology; pathogenesis; priority journal; protein analysis; protein expression; proteomics; review; Biological Science Disciplines; Disease; Gene Expression; Genome, Human; Human Genome Project; Humans; Mass Spectrometry; Proteome",,"Proteome",,,,"Gerstein, M.B., Architecture of the human regulatory network derived from ENCODE data (2012) Nature, 489 (7414), pp. 91-100; Dunham, I., An integrated encyclopedia of DNA elements in the human genome (2012) Nature, 489 (7414), pp. 57-74; Bensimon, A., Heck, A.J.R., Aebersold, R., Mass spectrometry-based proteomics and network biology (2012) Annu. Rev. Biochem., 81 (1), pp. 379-405; Hood, L.E., New and improved proteomics technologies for understanding complex biological systems: Addressing a grand challenge in the life sciences (2012) Proteomics, 12 (18), pp. 2773-2783; Nagaraj, N., Deep proteome and transcriptome mapping of a human cancer cell line (2011) Mol. Syst. Biol., p. 7; Beck, M., The quantitative proteome of a human cell line (2011) Mol. Syst. Biol., 7, p. 549; Munoz, J., The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells (2011) Mol. Syst. Biol., 7, p. 550; Vidal, M., The human proteome-A scientific opportunity for transforming diagnostics, therapeutics, and healthcare (2012) Clin. Proteomics, 9 (1), p. 6; Berglund, L., A gene centric Human Protein Atlas for expression profiles based on antibodies (2008) Mol. Cell. Proteomics, 7 (10), pp. 2019-2027; Legrain, P., The human proteome project: Current state and future direction (2011) Mol. Cell. Proteomics, , DOI: 10.1074/mcp.M111.009993-1; Farrah, T., A high-confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas (2011) Mol. Cell. Proteomics, 10 (9), pp. M110006353; Deutsch, E., Human plasma peptideatlas (2005) Proteomics, 5 (13), pp. 3497-3500; Picotti, P., A database of mass spectrometric assays for the yeast proteome (2008) Nat. Methods, 5 (11), pp. 913-914; Farrah, T., PASSEL: The peptideatlas srm experiment library (2012) Proteomics, 12, pp. 1170-1175; Uhlen, M., Towards knowledge-based human protein atlas (2010) Nat. Biotechnol., 8 (12), pp. 1248-1250; Edwards, A.M., Too many roads not taken (2011) Nature, 470 (7333), pp. 163-165; Isserlin, R., et al. Preprint at http://arxiv.org/abs/1102.0448v2, 2011Huttenhain, R., Reproducible quantification of cancerassociated proteins in body fluids using targeted proteomics (2012) Sci. Transl. Med., 4 (142), pp. 142ra94-142ra94; Polanski, M., Anderson, N.L., A list of candidate cancer biomarkers for targeted proteomics (2007) Biomarker Insights, 1, pp. 1-48; Zeiler, M., A Protein Epitope Signature Tag (PrEST) library allows SILAC-based absolute quantification and multiplexed determination of protein copy numbers in cell lines (2012) Mol. Cell. Proteomics, 11 (3), pp. O111009613; MacLean, B., Skyline: An open source document editor for creating and analyzing targeted proteomics experiments (2010) Bioinformatics, 26 (7), pp. 966-968; Brusniak, M.Y., ATAQS: A computational software tool for high throughput transition optimization and validation for selected reaction monitoring mass spectrometry (2011) BMC Bioinform., 12, p. 78; Reiter, L., MProphet: Automated data processing and statistical validation for large-scale SRM experiments (2011) Nat. Methods, 8, pp. 430-435; Chang, C.-Y., Protein significance analysis in selected reaction monitoring (SRM) measurements (2012) Mol. Cell. Proteomics, 11 (4), pp. M111014662; Gillet, L.C., Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: A new concept for consistent and accurate proteome analysis (2012) Mol. Cell. Proteomics, 11 (6), pp. O111016717","Aebersold, R.; Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland; email: aebersold@imsb.biol.ethz.ch",,,,,,,,15353893,,JPROB,10.1021/pr301151m,23259511,"English","J. Proteome Res.",Review,Scopus
"Ammar R., Torti D., Tsui K., Gebbia M., Durbic T., Bader G.D., Giaever G., Nislow C.","Chromatin is an ancient innovation conserved between Archaea and Eukarya",2012,"eLife",2012,1,,,,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84878965063&partnerID=40&md5=ebc41b6096a950cb369247ac47ebddc4","Department of Molecular Genetics, University of Toronto, Toronto, Canada; Donnelly Centre, University of Toronto, Toronto, Canada; Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada","Ammar, R., Department of Molecular Genetics, University of Toronto, Toronto, Canada, Donnelly Centre, University of Toronto, Toronto, Canada; Torti, D., Donnelly Centre, University of Toronto, Toronto, Canada; Tsui, K., Department of Molecular Genetics, University of Toronto, Toronto, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada; Gebbia, M., Department of Molecular Genetics, University of Toronto, Toronto, Canada, Donnelly Centre, University of Toronto, Toronto, Canada; Durbic, T., Donnelly Centre, University of Toronto, Toronto, Canada; Bader, G.D., Department of Molecular Genetics, University of Toronto, Toronto, Canada, Donnelly Centre, University of Toronto, Toronto, Canada; Giaever, G., Department of Molecular Genetics, University of Toronto, Toronto, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada; Nislow, C., Department of Molecular Genetics, University of Toronto, Toronto, Canada, Donnelly Centre, University of Toronto, Toronto, Canada","The eukaryotic nucleosome is the fundamental unit of chromatin, comprising a protein octamer that wraps ~147 bp of DNA and has essential roles in DNA compaction, replication and gene expression. Nucleosomes and chromatin have historically been considered to be unique to eukaryotes, yet studies of select archaea have identified homologs of histone proteins that assemble into tetrameric nucleosomes. Here we report the first archaeal genome-wide nucleosome occupancy map, as observed in the halophile Haloferax volcanii. Nucleosome occupancy was compared with gene expression by compiling a comprehensive transcriptome of Hfx. volcanii. We found that archaeal transcripts possess hallmarks of eukaryotic chromatin structure: nucleosome-depleted regions at transcriptional start sites and conserved -1 and +1 promoter nucleosomes. Our observations demonstrate that histones and chromatin architecture evolved before the divergence of Archaea and Eukarya, suggesting that the fundamental role of chromatin in the regulation of gene expression is ancient. © Ammar et al.",,,,,,,"20380, Canadian Cancer Society","Albert, I., Mavrich, T.N., Tomsho, L.P., Qi, J., Zanton, S.J., Schuster, S.C., Translational and rotational settings of H2A. Z nucleosomes across the Saccharomyces cerevisiae genome (2007) Nature, 446, pp. 572-576; Altman-Price, N., Mevarech, M., Genetic evidence for the importance of protein acetylation and protein deacetylation in the halophilic archaeon Haloferax volcanii (2009) J Bacteriol, 191, pp. 1610-1617; Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J., Basic local alignment search tool (1990) J Mol Biol, 215, pp. 403-410; Bailey, K.A., Pereira, S.L., Widom, J., Reeve, J.N., Archaeal histone selection of nucleosome positioning sequences and the procaryotic origin of histone-dependent genome evolution (2000) J Mol Biol, 303, pp. 25-34; Breuert, S., Allers, T., Spohn, G., Soppa, J., Regulated polyploidy in halophilic archaea (2006) PloS One, 1, pp. e92; Chang, G.S., Noegel, A.A., Mavrich, T.N., Muller, R., Tomsho, L.P., Ward, E., Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium (2012) Genome Res, 22, pp. 1098-1106; Chung, H.R., Dunkel, I., Heise, F., Linke, C., Krobitsch, S., Ehrenhofer-Murray, A.E., The effect of micrococcal nuclease digestion on nucleosome positioning data (2010) PloS One, 5, pp. e15754; David, L., Huber, W., Granovskaia, M., Toedling, J., Palm, C.J., Bofkin, L., A high-resolution map of transcription in the yeast genome (2006) Proc Natl Acad Sci USA, 103, pp. 5320-5325; DePristo, M.A., Banks, E., Poplin, R., Garimella, K.V., Maguire, J.R., Hartl, C., A framework for variation discovery and genotyping using next-generation DNA sequencing data (2011) Nat Genet, 43, pp. 491-498; Du, X., Takagi, H., N-Acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species (2007) Appl Microbiol Biotechnol, 75, pp. 1343-1351; Fiume, M., Williams, V., Brook, A., Brudno, M., Savant: Genome browser for high-throughput sequencing data (2010) Bioinformatics, 26, pp. 1938-1944; Forbes, A.J., Patrie, S.M., Taylor, G.K., Kim, Y.B., Jiang, L., Kelleher, N.L., Targeted analysis and discovery of posttranslational modifications in proteins from methanogenic archaea by top-down MS (2004) Proc Natl Acad Sci USA, 101, pp. 2678-2683; Geer, L.Y., Domrachev, M., Lipman, D.J., Bryant, S.H., CDART: Protein homology by domain architecture (2002) Genome Res, 12, pp. 1619-1623; Hartman, A.L., Norais, C., Badger, J.H., Delmas, S., Haldenby, S., Madupu, R., The complete genome sequence of Haloferax volcanii DS2, a model archaeon (2010) PloS One, 5, pp. e9605; He, S., Wurtzel, O., Singh, K., Froula, J.L., Yilmaz, S., Tringe, S.G., Validation of two ribosomal RNA removal methods for microbial metatranscriptomics (2010) Nat Methods, 7, pp. 807-812; Jiang, C., Pugh, B.F., Nucleosome positioning and gene regulation: Advances through genomics (2009) Nat Rev Genet, 10, pp. 161-172; Kaminska, K.H., Bujnicki, J.M., Bacteriophage Mu Mom protein responsible for DNA modification is a new member of the acyltransferase superfamily (2008) Cell Cycle, 7, pp. 120-121; Kaplan, N., Moore, I.K., Fondufe-Mittendorf, Y., Gossett, A.J., Tillo, D., Field, Y., The DNA-encoded nucleosome organization of a eukaryotic genome (2009) Nature, 458, pp. 362-366; Langmead, B., Salzberg, S.L., Fast gapped-read alignment with Bowtie 2 (2012) Nat Methods, 9, pp. 357-359; Lee, W., Tillo, D., Bray, N., Morse, R.H., Davis, R.W., Hughes, T.R., Nislow, C., A high-resolution atlas of nucleosome occupancy in yeast (2007) Nat Genet, 39, pp. 1235-1244; Marchler-Bauer, A., Lu, S., Anderson, J.B., Chitsaz, F., Derbyshire, M.K., Deweese-Scott, C., CDD: A conserved domain database for the functional annotation of proteins (2011) Nucleic Acids Res, 39, pp. D225-D229; McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data (2010) Genome Res, 20, pp. 1297-1303; Mullakhanbhai, M.F., Larsen, H., Halobacterium volcanii spec. nov., a Dead Sea halobacterium with a moderate salt requirement (1975) Arch Microbiol, 104, pp. 207-214; Palmer, J.R., Daniels, C.J., In vivo definition of an archaeal promoter (1995) J Bacteriol, 177, pp. 1844-1849; Pereira, S.L., Reeve, J.N., Histones and nucleosomes in Archaea and Eukarya: A comparative analysis (1998) Extremophiles, 2, pp. 141-148; Pereira, S.L., Grayling, R.A., Lurz, R., Reeve, J.N., Archaeal nucleosomes (1997) Proc Natl Acad Sci USA, 94, pp. 12633-12637; Puerta, C., Hernandez, F., Gutierrez, C., Pineiro, M., Lopez-Alarcon, L., Palacian, E., Efficient transcription of a DNA template associated with histone (H3. H4)2 tetramers (1993) J Biol Chem, 268, pp. 26663-26667; Rizzo, J.M., Mieczkowski, P.A., Buck, M.J., Tup1 stabilizes promoter nucleosome positioning and occupancy at transcriptionally plastic genes (2011) Nucleic Acids Res, 39, pp. 8803-8819; Sajan, S.A., Hawkins, R.D., Methods for identifying higher-order chromatin structure (2012) Annu Rev Genomics Hum Genet, 13, pp. 59-82; Sandman, K., Reeve, J.N., Archaeal histones and the origin of the histone fold (2006) Curr Opin Microbiol, 9, pp. 520-525; Sartorius-Neef, S., Pfeifer, F., In vivo studies on putative Shine-Dalgarno sequences of the halophilic archaeon Halobacterium salinarum (2004) Mol Microbiol, 51, pp. 579-588; Satchwell, S.C., Drew, H.R., Travers, A.A., Sequence periodicities in chicken nucleosome core DNA (1986) J Mol Biol, 191, pp. 659-675; Shivaswamy, S., Bhinge, A., Zhao, Y., Jones, S., Hirst, M., Iyer, V.R., Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation (2008) PLoS Biol, 6, pp. e65; Smith, S.W., (1997) The scientist and engineer's guide to digital signal processing, , San Diego: California Technical Pub; Talbert, P.B., Henikoff, S., Histone variants-ancient wrap artists of the epigenome (2010) Nat Rev Mol Cell Biol, 11, pp. 264-275; Trapnell, C., Pachter, L., Salzberg, S.L., TopHat: Discovering splice junctions with RNA-Seq (2009) Bioinformatics, 25, pp. 1105-1111; Tsui, K., Durbic, T., Gebbia, M., Nislow, C., Genomic approaches for determining nucleosome occupancy in yeast (2012) Methods Mol Biol, 833, pp. 389-411; Valouev, A., Johnson, S.M., Boyd, S.D., Smith, C.L., Fire, A.Z., Sidow, A., Determinants of nucleosome organization in primary human cells (2011) Nature, 474, pp. 516-520; Wurtzel, O., Sapra, R., Chen, F., Zhu, Y., Simmons, B.A., Sorek, R., A single-base resolution map of an archaeal transcriptome (2010) Genome Res, 20, pp. 133-141; Zhulidov, P.A., Bogdanova, E.A., Shcheglov, A.S., Vagner, L.L., Khaspekov, G.L., Kozhemyako, V.B., Simple cDNA normalization using kamchatka crab duplex-specific nuclease (2004) Nucleic Acids Res, 32, pp. e37","Nislow, C.; Department of Molecular Genetics, University of Toronto, Toronto, Canada; email: corey.nislow@gmail.com",,,,,,,,2050084X,,,10.7554/eLife.00078.001,,"English","eLife",Article,Scopus
"Lechman E.R., Gentner B., Van Galen P., Giustacchini A., Saini M., Boccalatte F.E., Hiramatsu H., Restuccia U., Bachi A., Voisin V., Bader G.D., Dick J.E., Naldini L.","Attenuation of miR-126 activity expands HSC in vivo without exhaustion",2012,"Cell Stem Cell",11,6,,799,811,,4,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84870894496&partnerID=40&md5=0a7339f0d300a83fb3a33b6fc4fd5a14","Campbell Family Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy, Milano 20132, Italy; Vita Salute San Raffaele University, Milano 20132, Italy; Division of Genetics and Cell Biology, Bimolecular Mass Spectrometry Unit, San Raffaele Scientific Institute, Milano 20132, Italy; Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan","Lechman, E.R., Campbell Family Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Gentner, B., Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy, Milano 20132, Italy, Vita Salute San Raffaele University, Milano 20132, Italy; Van Galen, P., Campbell Family Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Giustacchini, A., Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy, Milano 20132, Italy, Vita Salute San Raffaele University, Milano 20132, Italy; Saini, M., Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy, Milano 20132, Italy, Vita Salute San Raffaele University, Milano 20132, Italy; Boccalatte, F.E., Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy, Milano 20132, Italy, Vita Salute San Raffaele University, Milano 20132, Italy; Hiramatsu, H., Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Restuccia, U., Division of Genetics and Cell Biology, Bimolecular Mass Spectrometry Unit, San Raffaele Scientific Institute, Milano 20132, Italy; Bachi, A., Division of Genetics and Cell Biology, Bimolecular Mass Spectrometry Unit, San Raffaele Scientific Institute, Milano 20132, Italy; Voisin, V., Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Bader, G.D., Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Dick, J.E., Campbell Family Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1L7, Canada; Naldini, L., Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy, Milano 20132, Italy, Vita Salute San Raffaele University, Milano 20132, Italy","Lifelong blood cell production is governed through the poorly understood integration of cell-intrinsic and -extrinsic control of hematopoietic stem cell (HSC) quiescence and activation. MicroRNAs (miRNAs) coordinately regulate multiple targets within signaling networks, making them attractive candidate HSC regulators. We report that miR-126, a miRNA expressed in HSC and early progenitors, plays a pivotal role in restraining cell-cycle progression of HSC in vitro and in vivo. miR-126 knockdown by using lentiviral sponges increased HSC proliferation without inducing exhaustion, resulting in expansion of mouse and human long-term repopulating HSC. Conversely, enforced miR-126 expression impaired cell-cycle entry, leading to progressively reduced hematopoietic contribution. In HSC/early progenitors, miR-126 regulates multiple targets within the PI3K/AKT/GSK3β pathway, attenuating signal transduction in response to extrinsic signals. These data establish that miR-126 sets a threshold for HSC activation and thus governs HSC pool size, demonstrating the importance of miRNA in the control of HSC function. © 2012 Elsevier Inc.",,"glycogen synthase kinase 3beta; lentivirus vector; microRNA 126; protein kinase B; animal cell; animal experiment; animal tissue; article; cell activation; cell cycle progression; cell expansion; cell function; cell proliferation; controlled study; gene pool; gene silencing; hematopoietic stem cell; human; human cell; in vitro study; in vivo study; mouse; nonhuman; priority journal; signal transduction",,"protein kinase B, 148640-14-6",,,,"Bartel, D.P., MicroRNAs: Target recognition and regulatory functions (2009) Cell, 136, pp. 215-233; Buitenhuis, M., The role of PI3K/protein kinase B (PKB/c-akt) in migration and homing of hematopoietic stem and progenitor cells (2011) Curr. Opin. 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Cell, 15, pp. 261-271; Wilson, A., Laurenti, E., Oser, G., Van Der Wath, R.C., Blanco-Bose, W., Jaworski, M., Offner, S., Bockamp, E., Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair (2008) Cell, 135, pp. 1118-1129; Yilmaz, Ö.H., Valdez, R., Theisen, B.K., Guo, W., Ferguson, D.O., Wu, H., Morrison, S.J., Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells (2006) Nature, 441, pp. 475-482; Zhang, J., Du, Y.-Y., Lin, Y.-F., Chen, Y.-T., Yang, L., Wang, H.-J., Ma, D., The cell growth suppressor, mir-126, targets IRS-1 (2008) Biochem. Biophys. Res. Commun., 377, pp. 136-140","Dick, J.E.; Campbell Family Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; email: jdick@uhnresearch.ca",,,,,,,,19345909,,,10.1016/j.stem.2012.09.001,,"English","Cell Stem Cell",Article,Scopus
"Saito R., Smoot M.E., Ono K., Ruscheinski J., Wang P.-L., Lotia S., Pico A.R., Bader G.D., Ideker T.","A travel guide to Cytoscape plugins",2012,"Nature Methods",9,11,,1069,1076,,3,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84869054051&partnerID=40&md5=193093add4188a039d00560bece8ede3","Department of Medicine, University of California, San Diego, CA, United States; Department of Bioengineering, University of California, San Diego, CA, United States; Gladstone Institutes, San Francisco, CA, United States; Donnelly Centre, Faculty of Medicine, University of Toronto, Toronto, ON, Canada","Saito, R., Department of Medicine, University of California, San Diego, CA, United States, Department of Bioengineering, University of California, San Diego, CA, United States; Smoot, M.E., Department of Medicine, University of California, San Diego, CA, United States, Department of Bioengineering, University of California, San Diego, CA, United States; Ono, K., Department of Medicine, University of California, San Diego, CA, United States, Department of Bioengineering, University of California, San Diego, CA, United States; Ruscheinski, J., Department of Medicine, University of California, San Diego, CA, United States, Department of Bioengineering, University of California, San Diego, CA, United States; Wang, P.-L., Department of Medicine, University of California, San Diego, CA, United States, Department of Bioengineering, University of California, San Diego, CA, United States; Lotia, S., Gladstone Institutes, San Francisco, CA, United States; Pico, A.R., Gladstone Institutes, San Francisco, CA, United States; Bader, G.D., Donnelly Centre, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Ideker, T., Department of Medicine, University of California, San Diego, CA, United States, Department of Bioengineering, University of California, San Diego, CA, United States","Cytoscape is open-source software for integration, visualization and analysis of biological networks. It can be extended through Cytoscape plugins, enabling a broad community of scientists to contribute useful features. This growth has occurred organically through the independent efforts of diverse authors, yielding a powerful but heterogeneous set of tools. We present a travel guide to the world of plugins, covering the 152 publicly available plugins for Cytoscape 2.5-2.8. We also describe ongoing efforts to distribute, organize and maintain the quality of the collection. © 2012 Nature America, Inc. All rights reserved.",,"computer interface; computer network; computer program; computer terminal; cytoscape; data storage device; human computer interaction; information retrieval; molecular biology; molecular genetics; plugin; priority journal; protein protein interaction; review; systems biology; Algorithms; Computational Biology; Computer Simulation; Data Mining; Database Management Systems; Gene Expression Profiling; Gene Regulatory Networks; Genes; Genomics; Models, Biological; Software",,,,,,"Cline, M.S., Integration of biological networks and gene expression data using Cytoscape (2007) Nat. 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"Alshalalfa M., Bader G.D., Goldenberg A., Morris Q., Alhajj R.","Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study",2012,"BMC Systems Biology",6,, 112,,,,1,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84865322800&partnerID=40&md5=b6b50aa537dd5a27b15d2ef088803df6","Department of Computer Science, University of Calgary, Calgary, AB, Canada; The Donnelly Centre, University of Toronto, The Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Genetics and Genome Biology, Toronto, Canada; Biotechnology Research Centre, Palestine Polytechnic University, Hebron, Palestine","Alshalalfa, M., Department of Computer Science, University of Calgary, Calgary, AB, Canada, Biotechnology Research Centre, Palestine Polytechnic University, Hebron, Palestine; Bader, G.D., The Donnelly Centre, University of Toronto, The Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Goldenberg, A., Genetics and Genome Biology, Toronto, Canada; Morris, Q., The Donnelly Centre, University of Toronto, The Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Alhajj, R., Department of Computer Science, University of Calgary, Calgary, AB, Canada","Background: The use of biological molecular network information for diagnostic and prognostic purposes and elucidation of molecular disease mechanism is a key objective in systems biomedicine. The network of regulatory miRNA-target and functional protein interactions is a rich source of information to elucidate the function and the prognostic value of miRNAs in cancer. The objective of this study is to identify miRNAs that have high influence on target protein complexes in prostate cancer as a case study. This could provide biomarkers or therapeutic targets relevant for prostate cancer treatment.Results: Our findings demonstrate that a miRNA's functional role can be explained by its target protein connectivity within a physical and functional interaction network. To detect miRNAs with high influence on target protein modules, we integrated miRNA and mRNA expression profiles with a sequence based miRNA-target network and human functional and physical protein interactions (FPI). miRNAs with high influence on target protein complexes play a role in prostate cancer progression and are promising diagnostic or prognostic biomarkers. We uncovered several miRNA-regulated protein modules which were enriched in focal adhesion and prostate cancer genes. Several miRNAs such as miR-96, miR-182, and miR-143 demonstrated high influence on their target protein complexes and could explain most of the gene expression changes in our analyzed prostate cancer data set.Conclusions: We describe a novel method to identify active miRNA-target modules relevant to prostate cancer progression and outcome. miRNAs with high influence on protein networks are valuable biomarkers that can be used in clinical investigations for prostate cancer treatment. © 2012 Alshalalfa et al.; licensee BioMed Central Ltd.","High-influence miRNA; MiRNA; Protein interactions; Systems biology","microRNA; tumor marker; article; biology; gene expression regulation; genetics; human; male; metabolism; methodology; pathology; prognosis; prostate tumor; protein analysis; protein protein interaction; recurrent disease; Computational Biology; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Prognosis; Prostatic Neoplasms; Protein Interaction Mapping; Protein Interaction Maps; 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"Reimand J., Hui S., Jain S., Law B., Bader G.D.","Domain-mediated protein interaction prediction: From genome to network",2012,"FEBS Letters",586,17,,2751,2763,,4,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84864579478&partnerID=40&md5=de15bc47f18f814f348c32268c7734a9","Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Computer Science, University of Toronto, 10 King's College Circle, Toronto, ON M5S 3G4, Canada","Reimand, J., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Hui, S., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Jain, S., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, 10 King's College Circle, Toronto, ON M5S 3G4, Canada; Law, B., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, 10 King's College Circle, Toronto, ON M5S 3G4, Canada; Bader, G.D., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada, Department of Computer Science, University of Toronto, 10 King's College Circle, Toronto, ON M5S 3G4, Canada","Protein-protein interactions (PPIs), involved in many biological processes such as cellular signaling, are ultimately encoded in the genome. Solving the problem of predicting protein interactions from the genome sequence will lead to increased understanding of complex networks, evolution and human disease. We can learn the relationship between genomes and networks by focusing on an easily approachable subset of high-resolution protein interactions that are mediated by peptide recognition modules (PRMs) such as PDZ, WW and SH3 domains. This review focuses on computational prediction and analysis of PRM-mediated networks and discusses sequence- and structure-based interaction predictors, techniques and datasets for identifying physiologically relevant PPIs, and interpreting high-resolution interaction networks in the context of evolution and human disease. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. 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"Northcott P.A., Shih D.J.H., Peacock J., Garzia L., Sorana Morrissy A., Zichner T., Stutz A.M., Korshunov A., Reimand J., Schumacher S.E., Beroukhim R., Ellison D.W., Marshall C.R., Lionel A.C., MacK S., Dubuc A., Yao Y., Ramaswamy V., Luu B., Rolider A., Cavalli F.M.G., Wang X., Remke M., Wu X., Chiu R.Y.B., Chu A., Chuah E., Corbett R.D., Hoad G.R., Jackman S.D., Li Y., Lo A., Mungall K.L., Ming Nip K., Qian J.Q., Raymond A.G.J., Thiessen N., Varhol R.J., Birol I., Moore R.A., Mungall A.J., Holt R., Kawauchi D., Roussel M.F., Kool M., Jones D.T.W., Witt H., Fernandez-L A., Kenney A.M., Wechsler-Reya R.J., Dirks P., Aviv T., Grajkowska W.A., Perek-Polnik M., Haberler C.C., Delattre O., Reynaud S.S., Doz F.F., Pernet-Fattet S.S., Cho B.-K., Kim S.-K., Wang K.-C., Scheurlen W., Eberhart C.G., Fevre-Montange M., Jouvet A., Pollack I.F., Fan X., Muraszko K.M., Yancey Gillespie G., Di Rocco C., Massimi L., Michiels E.M.C., Kloosterhof N.K., French P.J., Kros J.M., Olson J.M., Ellenbogen R.G., Zitterbart K., Kren L., Thompson R.C., Cooper M.K., Lach B., McLendon R.E., Bigner D.D., Fontebasso A., Albrecht S., Jabado N., Lindsey J.C., Bailey S., Gupta N., Weiss W.A., Bognar L., Klekner A., Van Meter T.E., Kumabe T., Tominaga T., Elbabaa S.K., Leonard J.R., Rubin J.B., Liau L.M., Van Meir E.G., Fouladi M., Nakamura H., Cinalli G., Garami M., Hauser P., Saad A.G., Iolascon A., Jung S., Carlotti C.G., Vibhakar R., Shin Ra Y., Robinson S., Zollo M., Faria C.C., Chan J.A., Levy M.L., Sorensen P.H.B., Meyerson M., Pomeroy S.L., Cho Y.-J., Bader G.D., Tabori U., Hawkins C.E., Bouffet E., Scherer S.W., Rutka J.T., Malkin D., Clifford S.C., Jones S.J.M., Korbel J.O., Pfister S.M., Marra M.A., Taylor M.D.","Subgroup-specific structural variation across 1,000 medulloblastoma genomes",2012,"Nature",487,7409,,49,56,,29,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84864425646&partnerID=40&md5=fb69f1368e339aad824be514ee8fe6b2","Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany; CCU Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 220-221, Germany; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States; Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, United States; Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States; Cancer Program, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, United States; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States; Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States; McLaughlin Centre, Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada; Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Tumour Cell Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States; Department of Pediatric Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Departments of Hematology and Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Pediatric Clinical Trials Office, Memorial Sloan-Kettering Cancer Center, 405 Lexington Avenue, New York, NY 10174, United States; Neurological Surgery, Vanderbilt Medical Center, T-4224 MCN, Nashville, TN 37232-2380, United States; Cancer Biology, Vanderbilt Medical Center, MRB III 6160, 465 21st Avenue South, Nashville, TN 37232-8550, United States; Sanford-BurnhamMedical Research Institute, San Diego, CA 92037, United States; Department of Surgery, Division of Neurosurgery and Labatt Brain Tumour Research Centre, Hospital for Sick Children, 555 University Avenue, Hill 1503, Toronto, ON M5G 1X8, Canada; Developmental and Stem Cell Biology Program, Hospital for Sick Children, TMDT-13-601, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Pathology, Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland; Department of Oncology, Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland; Institute of Neurology, Medical University of Vienna, AKH 4J, Waehringer Gürtel 18-20, A-1097 Vienna, Austria; INSERMU 830, Institut Curie, 26 rue d'Ulm, 75238 Paris Cedex 5, France; Unit of Somatic Genetics, Institut Curie, 26 rue d'Ulm, 75238 Paris Cedex 5, France; Department of Pediatric Oncology, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 5, France; Pediatric Hematology and Oncology, CHUV University Hospital, 1011 Lausanne, Switzerland; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, 101 Daehak-Ro Jongno-Gu, Seoul 110-744, South Korea; Cnopf́sche Kinderklinik, Theodor-Kutzer-Ufer 1-3, 90419 Nuremberg, Germany; Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Ross Building 558, 720 Rutland Avenue, Baltimore, MD 21205, United States; INSERM U1028, CNRS UMR5292, Université de Lyon, 69336 Lyon, France; Centre de Pathologie EST, Groupement Hospitalier EST, Universite de Lyon, 69500 Bron, France; Department of Neurological Surgery, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, United States; Departments of Neurosurgery and Cell and Developmental Biology, University of Michigan Medical School, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, United States; Department of Neurosurgery, University of Michigan Medical School, Taubman Center, 1500 E.Medical Center Drive, Ann Arbor, MI 48109, United States; Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AB 35294-0006, United States; Department of Pediatric Neurosurgery, Catholic University Medical School, 00186 Rome, Italy; Department of Pediatric Oncology and Hematology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 Rotterdam, Netherlands; Department of Neurology, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 CA Rotterdam, Netherlands; Department of Pathology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands; Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, United States; Seattle Children's Hospital, Seattle, WA 98104, United States; Neurological Surgery, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98104, United States; Department of Pediatric Oncology, School of Medicine, Masaryk University, Cernopolni 9, 613 00 Brno, Czech Republic; Department of Pediatric Oncology, University Hospital Brno, 625 00 Brno, Czech Republic; Department of Pathology, University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic; Department of Neurology, Vanderbilt Medical Center, MRB III 6160, 465 21st Avenue South, Nashville, TN 37232-8550, United States; Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMasterUniversity, Hamilton, ON L8S4L8, Canada; Department of Pathologyand Laboratory Medicine, Hamilton General Hospital, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada; Department of Pathology, Duke University, DUMC 3712, Durham, NC 27710, United States; Division of Experimental Medicine, McGill University, 4060 Ste Catherine West, Montreal, QC H3Z 2Z3, Canada; Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada; Department of Pathology, Montreal Children's Hospital, 2300 Tupper, Montreal, QC H3H 1P3, Canada; Department of Pediatrics, Division of Hemato-Oncology, McGill University, Montreal, QC H3H1P3, Canada; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, United Kingdom; Departments of Neurological Surgery and Pediatrics, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0112, United States; Departments of Neurology, Pediatrics, and Neurosurgery, University of California San Francisco, Helen Diller Family Cancer Research Building, 1450 3rd Street, San Francisco, CA 94158, United States; Department of Neurosurgery, University of Debrecen, Medical and Health Science Centre, Móricz Zs. Krt. 22., 4032 Debrecen, Hungary; Pediatrics, Virginia Commonwealthy University, School of Medicine, Box 980646, Pediatric Hematology-Oncology, 1101 East Marshall Street, Richmond, VA 23298-0646, United States; Department OfNeurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; Department of Neurosurgery, Division of Pediatric Neurosurgery, St Louis University School of Medicine, 1465 South Grand Boulevard, St Louis, MO 63104, United States; Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St Louis Children's Hospital, 660 South Euclid Avenue, St Louis, MO 63110, United States; Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, Campus Box 8208, 660 South Euclid Avenue, St Louis, MO 63110, United States; Department of Neurosurgery, David Geffen School of Medicine at UCLA, Campus 690118, 10833 Le Conte Avenue, Los Angeles, CA 90095, United States; Laboratory of Molecular Neuro-Oncology, Departments of Neurosurgery and Hematology and MedicalOncology, Emory University, 1365C Clifton Road NE, Atlanta, GA 30322, United States; Division of Oncology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, 1-1-1, Honjo, Kumamoto 860-8556, Japan; Paediatric Neurosurgery, Ospedale Santobono-Pausilipon, 80145 Naples, Italy; 2nd Department of Pediatrics, Semmelweis University, 1085 Budapest, Hungary; Department of Pathology, University of Arkansas for Medical Sciences, 1 Children's Way, Little Rock, AR 72202, United States; Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples, Via Pansini 5, 80145 Naples, Italy; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy; Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Chonnam 519-763, South Korea; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900, Rebeirao Preto, São Paulo, Brazil; Department of Pediatrics, University of Colorado Denver, 12800 19th Avenue, Aurora, CO 80045, United States; Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, 138-736, South Korea; Division of Pediatric Neurosurgery, Case Western Reserve, Cleveland, OH 44106, United States; Rainbow Babies and Children's, Cleveland, OH 44106, United States; Division of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte EPE, 1169-050, Lisbon, Portugal; Cell Biology Program, Hospital for Sick Children, TMDT-401-J, 101 College Street, Toronto, ON M5G1L7, Canada; Department of Pathology, Laboratory Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada; UCSD Division of Neurosurgery, Rady Children's Hospital San Diego, 8010 Frost Street, San Diego, CA 92123, United States; Department of Molecular Oncology, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Neurology, Harvard Medical School, Children's Hospital Boston, Fegan 11, 300 Longwood Avenue, Boston, MA 02115, United States; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, MSLS Building, 1201 Welch Road, Stanford, CA 94305, United States; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto M5G1X5, ON, Canada; Department of Haematology and Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Pathology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Department of Medical Genetics, University of British Columbia, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada","Northcott, P.A., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Shih, D.J.H., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Peacock, J., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Garzia, L., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Sorana Morrissy, A., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Zichner, T., Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Stútz, A.M., Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Korshunov, A., CCU Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 220-221, Germany; Reimand, J., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Schumacher, S.E., Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States; Beroukhim, R., Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States, Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, United States, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States, Cancer Program, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, United States, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States; Ellison, D.W., Department of Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, United States; Marshall, C.R., McLaughlin Centre, Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada; Lionel, A.C., Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; MacK, S., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Dubuc, A., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Yao, Y., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Ramaswamy, V., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Luu, B., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Rolider, A., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Cavalli, F.M.G., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Wang, X., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Remke, M., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Wu, X., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Chiu, R.Y.B., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Chu, A., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Chuah, E., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Corbett, R.D., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Hoad, G.R., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Jackman, S.D., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; 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Cho, Y.-J., Department of Neurology and Neurological Sciences, Stanford University School of Medicine, MSLS Building, 1201 Welch Road, Stanford, CA 94305, United States; Bader, G.D., Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, McLaughlin Centre, Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto M5G1X5, ON, Canada; Tabori, U., Department of Haematology and Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Hawkins, C.E., Department of Pathology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Bouffet, E., Department of Haematology and Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Scherer, S.W., McLaughlin Centre, Department of Molecular Genetics, University of Toronto, 101 College Street, Toronto, ON M5G 1L7, Canada, Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada; Rutka, J.T., Department of Surgery, Division of Neurosurgery and Labatt Brain Tumour Research Centre, Hospital for Sick Children, 555 University Avenue, Hill 1503, Toronto, ON M5G 1X8, Canada; Malkin, D., Department of Haematology and Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada, Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Clifford, S.C., Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE1 4LP, United Kingdom; Jones, S.J.M., Michael Smith Genome Sciences Centre, BC Cancer Agency, 100-570 West 7th Avenue, Vancouver, BC V5Z 4S6, Canada; Korbel, J.O., Genome Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Pfister, S.M., Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, Department of Pediatric Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany; Marra, M.A., Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada, Department of Medical Genetics, University of British Columbia, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Taylor, M.D., Developmental and StemCell Biology Program, Hospital for Sick Children, 101 College Street, Toronto, ON M5G 1L7, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Buildings, 1 King's College Circle, Toronto, ON M5S 1A8, Canada, Department of Surgery, Division of Neurosurgery and Labatt Brain Tumour Research Centre, Hospital for Sick Children, 555 University Avenue, Hill 1503, Toronto, ON M5G 1X8, Canada","Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. 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"Labbe R.M., Irimia M., Currie K.W., Lin A., Zhu S.J., Brown D.D.R., Ross E.J., Voisin V., Bader G.D., Blencowe B.J., Pearson B.J.","A Comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals",2012,"Stem Cells",30,8,,1734,1745,,11,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84864376995&partnerID=40&md5=f44a304f5f9f5f26beabf1b3737944d1","Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada; Stowers Institute for Medical Research, Kansas City, MO, United States","Labbé, R.M., Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada, Ontario Institute for Cancer Research, Toronto, ON, Canada; Irimia, M., Donnelly Centre, University of Toronto, Toronto, ON, Canada; Currie, K.W., Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Lin, A., Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Zhu, S.J., Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Brown, D.D.R., Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Ross, E.J., Stowers Institute for Medical Research, Kansas City, MO, United States; Voisin, V., Donnelly Centre, University of Toronto, Toronto, ON, Canada; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Ontario Institute for Cancer Research, Toronto, ON, Canada; Blencowe, B.J., Donnelly Centre, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Pearson, B.J., Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Ontario Institute for Cancer Research, Toronto, ON, Canada","Many long-lived species of animals require the function of adult stem cells throughout their lives. However, the transcriptomes of stem cells in invertebrates and vertebrates have not been compared, and consequently, ancestral regulatory circuits that control stem cell populations remain poorly defined. In this study, we have used data from high-throughput RNA sequencing to compare the transcriptomes of pluripotent adult stem cells from planarians with the transcriptomes of human and mouse pluripotent embryonic stem cells. From a stringently defined set of 4,432 orthologs shared between planarians, mice and humans, we identified 123 conserved genes that are ≥5-fold differentially expressed in stem cells from all three species. Guided by this gene set, we used RNAi screening in adult planarians to discover novel stem cell regulators, which we found to affect the stem cell-associated functions of tissue homeostasis, regeneration, and stem cell maintenance. Examples of genes that disrupted these processes included the orthologs of TBL3, PSD12, TTC27, and RACK1. From these analyses, we concluded that by comparing stem cell transcriptomes from diverse species, it is possible to uncover conserved factors that function in stem cell biology. These results provide insights into which genes comprised the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency. © AlphaMed Press.","Adult stem cells; Deep sequencing; Evolution; Flatworm; Lophotrochozoan; Mammals; Planarians; Pluripotency; Schmidtea mediterranea","transcriptome; animal cell; article; comparative study; embryonic stem cell; gene; gene identification; genetic conservation; mammal; nonhuman; nucleotide sequence; pluripotent stem cell; psd12 gene; RACK1 gene; RNA interference; RNA sequence; tbl3 gene; transcriptomics; ttc27 gene; Turbellaria; Animals; Cell Differentiation; Gene Expression Profiling; Humans; Mammals; Mice; Planarians; Pluripotent Stem Cells; Animalia; Invertebrata; Lophotrochozoa; Mammalia; Mus; Platyhelminthes; Schmidtea mediterranea; Turbellaria; Vertebrata","GENBANK: GSE37910",,,,,"Simons, B.D., Clevers, H., Strategies for homeostatic stem cell self-renewal in adult tissues (2011) Cell, 145, pp. 851-862; Reya, T., Morrison, S.J., Clarke, M.F., Stem cells, cancer, and cancer stem cells (2011) Nature, 414, pp. 105-111; Noh, K.H., Lee, Y.H., Jeon, J.H., Cancer vaccination drives Nanog-dependent evolution of tumor cells toward an immune-resistant and stem-like phenotype (2012) Cancer Res, 72, pp. 1717-1727; Watanabe, H., Hoang, V.T., Mattner, R., Immortality and the base of multicellular life: Lessons from cnidarian stem cells (2009) Semin Cell Dev Biol, 20, pp. 1114-1125; Bosch, T.C., Hydra and the evolution of stem cells (2009) BioEssays, 31, pp. 478-486; Morgan, T.H., Experimental studies of the regeneration of Planaria maculata (1898) Arch Entw Mech Org, 7, pp. 364-397; Brøndsted, H.V., (1969) Planarian Regeneration, , 1st ed. 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Wu, J.Q., Habegger, L., Noisa, P., Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing (2010) Proc Natl Acad Sci USA, 107, pp. 5254-5259; Grabherr, M.G., Haas, B.J., Yassour, M., Full-length transcriptome assembly from RNA-Seq data without a reference genome (2011) Nat Biotechnol, 29, pp. 644-652; Langmead, B., Trapnell, C., Pop, M., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome (2009) Genome Biol, 10, pp. R25; Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Mesirov, J.P., Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles (2005) Proceedings of the National Academy of Sciences of the United States of America, 102 (43), pp. 15545-15550. , DOI 10.1073/pnas.0506580102; Merico, D., Isserlin, R., Bader, G.D., Visualizing gene-set enrichment results using the Cytoscape plug-in enrichment map (2011) Methods Mol Biol, 781, pp. 257-277; Merico, D., Isserlin, R., Stueker, O., Enrichment map: A network-based method for gene-set enrichment visualization and interpretation (2010) PLoS One, 5, pp. e13984; Sanchez, A.A., Newmark, P.A., Robb, S.M.C., Juste, R., The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration (2002) Development, 129 (24), pp. 5659-5665. , DOI 10.1242/dev.00167; Pearson, B.J., Eisenhoffer, G.T., Gurley, K.A., Formaldehyde-based whole-mount in situ hybridization method for planarians (2009) Dev Dyn, 238, pp. 443-450; Shackleton, M., Quintana, E., Fearon, E.R., Heterogeneity in cancer: Cancer stem cells versus clonal evolution (2009) Cell, 138, pp. 822-829; Reddien, P.W., Bermange, A.L., Murfitt, K.J., Jennings, J.R., Sanchez, A.A., Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria (2005) Developmental Cell, 8 (5), pp. 635-649. , DOI 10.1016/j.devcel.2005.02.014, PII S1534580705000924; 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Eppert, K., Takenaka, K., Lechman, E.R., Stem cell gene expression programs influence clinical outcome in human leukemia (2011) Nat Med, 17, pp. 1086-1093; Müller, F.J., Laurent, L.C., Kostka, D., Regulatory networks define phenotypic classes of human stem cell lines (2008) Nature, 455, pp. 401-405; Henras, A., Henry, Y., Bousquet-Antonelli, C., Noaillac-Depeyre, J., Gelugne, J.-P., Caizergues-Ferrer, M., Nhp2p and Nop10p are essential for the function of H/ACA snoRNPs (1998) EMBO Journal, 17 (23), pp. 7078-7090; Wang, F., Osawa, T., Tsuchida, R., Downregulation of receptor for activated C-kinase 1 (RACK1) suppresses tumor growth by inhibiting tumor cell proliferation and tumor-associated angiogenesis (2011) Cancer Sci, 102, pp. 2007-2013","Pearson, B.J.; Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, ON, Canada; email: bret.pearson@sickkids.ca",,,,,,,,10665099,,STCEE,10.1002/stem.1144,22696458,"English","Stem Cells",Article,Scopus
"Michaut M., Bader G.D.","Multiple genetic interaction experiments provide complementary information useful for gene function prediction",2012,"PLoS Computational Biology",8,6, e1002559,,,,2,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84864046645&partnerID=40&md5=b1d2f2d64e31686bcbbc2f3e7c0fc68c","The Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Computer Science, University of Toronto, Toronto, ON, Canada; Bioinformatics and Statistics Group, Netherlands Cancer Institute, Amsterdam, Netherlands","Michaut, M., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Bioinformatics and Statistics Group, Netherlands Cancer Institute, Amsterdam, Netherlands; Bader, G.D., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Computer Science, University of Toronto, Toronto, ON, Canada","Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens. © 2012 Michaut, Bader.",,"area under the curve; article; controlled study; fungal gene; fungal genetics; gene function; gene interaction; gene mapping; gene regulatory network; genetic screening; growth rate; molecular interaction; mutational analysis; nonhuman; phenotypic variation; prediction; quantitative analysis; receiver operating characteristic; Saccharomyces cerevisiae; biological model; biology; computer simulation; fungal genome; gene regulatory network; genetic epistasis; genetics; growth, development and aging; mutation; phenotype; Saccharomyces cerevisiae; Computational Biology; Computer Simulation; Epistasis, Genetic; Gene Regulatory Networks; Genome, Fungal; Models, Genetic; Mutation; Phenotype; Saccharomyces cerevisiae",,,,,,"Mani, R., St Onge, R.P., Hartman, J.L., Giaever, G., Roth, F.P., Defining genetic interaction (2008) Proc Natl Acad Sci U S A, 105, p. 3461; 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Bandyopadhyay, S., Mehta, M., Kuo, D., Sung, M.-K., Chuang, R., Rewiring of genetic networks in response to DNA damage (2010) Science, 330, p. 1385; Batenchuk, C., Tepliakova, L., Kaern, M., Identification of response-modulated genetic interactions by sensitivity-based epistatic analysis (2010) BMC Genomics, 11, p. 493; Carter, G.W., Galas, D.J., Galitski, T., Maximal extraction of biological information from genetic interaction data (2009) PLoS Comput Biol, 5, pp. e1000347; Drees, B.L., Thorsson, V., Carter, G.W., Rives, A.W., Raymond, M.Z., Derivation of genetic interaction networks from quantitative phenotype data (2005) Genome Biol, 6, pp. R38; Carter, G.W., Prinz, S., Neou, C., Shalby, J.P., Marzolf, B., Prediction of phenotype and gene expression for combinations of mutations (2007) Mol Syst Biol, 3, p. 96; Jonikas, M.C., Collins, S.R., Denic, V., Oh, E., Quan, E.M., Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum (2009) Science, 323, p. 1693; Collins, S.R., Miller, K.M., Maas, N.L., Roguev, A., Fillingham, J., Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map (2007) Nature, 446, p. 806; Schuldiner, M., Collins, S.R., Thompson, N.J., Denic, V., Bhamidipati, A., Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile (2005) Cell, 123, p. 507; Chiang, T., Scholtens, D., Sarkar, D., Gentleman, R., Huber, W., Coverage and error models of protein-protein interaction data by directed graph analysis (2007) Genome Biol, 8, pp. R186; Tong, A.H., Lesage, G., Bader, G.D., Ding, H., Xu, H., Global mapping of the yeast genetic interaction network (2004) Science, 303, p. 808; Mostafavi, S., Ray, D., Warde-Farley, D., Grouios, C., Morris, Q., GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function (2008) Genome Biol, 9, pp. S4; Montojo, J., Zuberi, K., Rodriguez, H., Kazi, F., Wright, G., GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop (2010) Bioinformatics, 26, p. 2927; Harris, M.A., Clark, J., Ireland, A., Lomax, J., Ashburner, M., The Gene Ontology (GO) database and informatics resource (2004) Nucleic Acids Res, 32, pp. D258; Baryshnikova, A., Costanzo, M., Kim, Y., Ding, H., Koh, J., Quantitative analysis of fitness and genetic interactions in yeast on a genome scale (2010) Nat Methods, 7, p. 1017; Lee, H.K., Hsu, A.K., Sajdak, J., Qin, J., Pavlidis, P., Coexpression analysis of human genes across many microarray data sets (2004) Genome Res, 14, p. 1085; Butland, G., Babu, M., Diaz-Mejia, J.J., Bohdana, F., Phanse, S., eSGA: E. coli synthetic genetic array analysis (2008) Nat Methods, 5, p. 789; Dixon, S.J., Fedyshyn, Y., Koh, J.L., Prasad, T.S., Chahwan, C., Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes (2008) Proc Natl Acad Sci U S A, 105, p. 16653; Roguev, A., Wiren, M., Weissman, J.S., Krogan, N.J., High-throughput genetic interaction mapping in the fission yeast Schizosaccharomyces pombe (2008) Nat Methods, 4, p. 861; 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Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Cytoscape: a software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, p. 2498","Bader, G. D.; The Donnelly Centre, University of Toronto, Toronto, ON, Canada; email: gary.bader@utoronto.ca",,,,,,,,1553734X,,,10.1371/journal.pcbi.1002559,22737063,"English","PLoS Comput. Biol.",Article,Scopus
"Liu J.C., Voisin V., Bader G.D., Deng T., Pusztai L., Symmans W.F., Esteva F.J., Egan S.E., Zacksenhaus E.","Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2 +:ERα - breast cancer",2012,"Proceedings of the National Academy of Sciences of the United States of America",109,15,,5832,5837,,6,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84859567448&partnerID=40&md5=84ad5e38e1844457e1df8fb3a902c3a4","Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, ON M5G 2M9, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, United States; Department of Pathology, MD Anderson Cancer Center, Houston, TX 77030, United States; Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M1, Canada","Liu, J.C., Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, ON M5G 2M9, Canada; Voisin, V., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Deng, T., Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, ON M5G 2M9, Canada; Pusztai, L., Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, United States; Symmans, W.F., Department of Pathology, MD Anderson Cancer Center, Houston, TX 77030, United States; Esteva, F.J., Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, United States; Egan, S.E., Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Zacksenhaus, E., Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, ON M5G 2M9, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada, Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M1, Canada","Human Epidermal Growth Factor Receptor 2-positive (HER2 +) breast cancer (BC) is a highly aggressive disease commonly treated with chemotherapy and anti-HER2 drugs, including trastuzumab. There is currently noway to predictwhich HER2 + BC patients will benefit from these treatments. Previous prognostic signatures for HER2 + BC were developed irrespective of the subtype or the hierarchical organization of cancer in which only a fraction of cells, tumor-initiating cells (TICs), can sustain tumor growth.Here,we used serial dilution and single-cell transplantation assays to identify MMTV-Her2/Neu mousemammary TICs as CD24 +:JAG1 - at a frequency of 2-4.5%. A 17-gene Her2-TIC-enriched signature (HTICS), generated on the basis of differentially expressed genes in TIC versus non-TIC fractions and trained on one HER2 + BC cohort, predicted clinical outcome onmultiple independent HER2 + cohorts. HTICS included up-regulated genes involved in S/G2/M transition and down-regulated genes involved in immune response. Its prognostic power was independent of other predictors, stratified lymph node + HER2 + BC into low and high-risk subgroups, and was specific for HER2 +:estrogen receptor alpha-negative (ERα -) patients (10-y overall survival of 83.6% for HTICS - and 24.0% for HTICS + tumors; hazard ratio = 5.57; P = 0.002). Whereas HTICS was specific to HER2 +:ERα - tumors, a previously reported stroma-derived signature was predictive for HER2 +:ERα + BC. Retrospective analyses revealed that patients with HTICS + HER2 +:ERα - tumors resisted chemotherapy but responded to chemotherapy plus trastuzumab. HTICS is, therefore, a powerful prognostic signature for HER2 +:ERα - BC that can be used to identify high risk patients that would benefit from anti-HER2 therapy.","Cancer stem cells; HER2 + breast cancer; Mouse models; Prognostic signature","CD24 antigen; epidermal growth factor receptor 2; estrogen receptor alpha; trastuzumab; animal experiment; animal model; article; breast cancer; cancer chemotherapy; cancer prognosis; cancer stem cell; cell assay; cell cycle G2 phase; cell cycle M phase; cell cycle S phase; cell fractionation; cell transplantation; controlled study; down regulation; female; gene expression; gene expression regulation; gene signature; hazard ratio; high risk patient; human; human cell; immune response; mouse; nonhuman; nucleotide sequence; overall survival; phase transition; priority journal; retrospective study; survival time; upregulation; Animals; Antibodies, Monoclonal, Humanized; Antigens, CD24; Antineoplastic Agents; Breast Neoplasms; Calcium-Binding Proteins; Cell Differentiation; Cell Division; Estrogen Receptor alpha; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Mice; Neoadjuvant Therapy; Neoplastic Stem Cells; Prognosis; Receptor, erbB-2; Signal Transduction; Treatment Outcome; Mouse mammary tumor virus","GENBANK: GSE22358","epidermal growth factor receptor 2, 137632-09-8; trastuzumab, 180288-69-1; Antibodies, Monoclonal, Humanized; Antigens, CD24; Antineoplastic Agents; Calcium-Binding Proteins; Estrogen Receptor alpha; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Receptor, erbB-2, 2.7.10.1; Serrate proteins, 134324-36-0; estrogen receptor alpha, human; trastuzumab",,,,"Slamon, D.J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Norton, L., Use of chemotherapy plus a monoclonal antibody against her2 for metastatic breast cancer that overexpresses HER2 (2001) New England Journal of Medicine, 344 (11), pp. 783-792. , DOI 10.1056/NEJM200103153441101; Abramson, V., Arteaga, C.L., New strategies in HER2-overexpressing breast cancer: Many combinations of targeted drugs available (2011) Clin Cancer Res, 17, pp. 952-958; Dean-Colomb, W., Esteva, F.J., Her2-positive breast cancer: Herceptin and beyond (2008) Eur J Cancer, 44, pp. 2806-2812; Gianni, L., Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: A 4-year follow-up of a randomised controlled trial (2011) Lancet Oncol, 12, pp. 236-244. , Herceptin Adjuvant (HERA) Trial Study Team; Martín, M., Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: Review and expert recommendations (2009) Oncologist, 14, pp. 1-11; O'Brien, C.A., Kreso, A., Dick, J.E., Cancer stem cells in solid tumors: An overview (2009) Semin Radiat Oncol, 19, pp. 71-77; Cicalese, A., The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells (2009) Cell, 138, pp. 1083-1095; Korkaya, H., Paulson, A., Iovino, F., Wicha, M.S., HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion (2008) Oncogene, 27, pp. 6120-6130; Desmedt, C., Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes (2008) Clin Cancer Res, 14, pp. 5158-5165; Paik, S., Shak, S., Tang, G., Kim, C., Baker, J., Cronin, M., Baehner, F.L., Wolmark, N., A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer (2004) New England Journal of Medicine, 351 (27), pp. 2817-2826. , DOI 10.1056/NEJMoa041588; Liu, R., Wang, X., Chen, G.Y., Dalerba, P., Gurney, A., Hoey, T., Sherlock, G., Clarke, M.F., The prognostic role of a gene signature from tumorigenic breast-cancer cells (2007) New England Journal of Medicine, 356 (3), pp. 217-226. , http://content.nejm.org/cgi/reprint/356/3/217.pdf, DOI 10.1056/NEJMoa063994; Finak, G., Bertos, N., Pepin, F., Sadekova, S., Souleimanova, M., Zhao, H., Chen, H., Park, M., Stromal gene expression predicts clinical outcome in breast cancer (2008) Nature Medicine, 14 (5), pp. 518-527. , DOI 10.1038/nm1764, PII NM1764; Guy, C.T., Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease (1992) Proc Natl Acad Sci USA, 89, pp. 10578-10582; Liu, J.C., Deng, T., Lehal, R.S., Kim, J., Zacksenhaus, E., Identification of tumorsphere- and tumor-initiating cells in HER2/Neu-induced mammary tumors (2007) Cancer Research, 67 (18), pp. 8671-8681. , http://cancerres.aacrjournals.org/cgi/reprint/67/18/8671, DOI 10.1158/0008-5472.CAN-07-1486; Vaillant, F., The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis (2008) Cancer Res, 68, pp. 7711-7717; Reedijk, M., Odorcic, S., Chang, L., Zhang, H., Miller, N., McCready, D.R., Lockwood, G., Sean, E., High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival (2005) Cancer Research, 65 (18), pp. 8530-8537. , DOI 10.1158/0008-5472.CAN-05-1069; Osipo, C., ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor (2008) Oncogene, 27, pp. 5019-5032; Muller, W.J., Sinn, E., Pattengale, P.K., Wallace, R., Leder, P., Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene (1988) Cell, 54, pp. 105-115; Kmieciak, M., Knutson, K.L., Dumur, C.I., Manjili, M.H., HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responses (2007) European Journal of Immunology, 37 (3), pp. 675-685. , DOI 10.1002/eji.200636639; Notta, F., Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells (2011) Nature, 469, pp. 362-367; Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Mesirov, J.P., Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles (2005) Proceedings of the National Academy of Sciences of the United States of America, 102 (43), pp. 15545-15550. , DOI 10.1073/pnas.0506580102; Merico, D., Isserlin, R., Stueker, O., Emili, A., Bader, G.D., Enrichment map: A network-based method for gene-set enrichment visualization and interpretation (2010) PLoS ONE, 5, pp. e13984; Staaf, J., Identification of subtypes in human epidermal growth factor receptor 2 - Positive breast cancer reveals a gene signature prognostic of outcome (2010) J Clin Oncol, 28, pp. 1813-1820; Shirley, S.H., Transcriptional regulation of estrogen receptor-alpha by p53 in human breast cancer cells (2009) Cancer Res, 69, pp. 3405-3414; Whitfield, M.L., George, L.K., Grant, G.D., Perou, C.M., Common markers of proliferation (2006) Nature Reviews Cancer, 6 (2), pp. 99-106. , DOI 10.1038/nrc1802, PII N1802; Glück, S., TP53 genomics predict higher clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine ±trastuzumab (2011) Breast Cancer Res Treat, , 10.1007/s10549-011-1412-7; Valastyan, S., Weinberg, R.A., Tumor metastasis: Molecular insights and evolving paradigms (2011) Cell, 147, pp. 275-292; Geiss, G.K., Bumgarner, R.E., Birditt, B., Dahl, T., Dowidar, N., Dunaway, D.L., Fell, H.P., Hood, L., Direct multiplexed measurement of gene expression with color-coded probe pairs (2008) Nature Biotechnology, 26 (3), pp. 317-325. , DOI 10.1038/nbt1385, PII NBT1385; Jiang, Z., Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status (2010) J Clin Invest, 120, pp. 3296-3309","Zacksenhaus, E.; Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, ON M5G 2M9, Canada; email: eldad.zacksenhaus@utoronto.ca",,,,,,,,00278424,,PNASA,10.1073/pnas.1201105109,22460789,"English","Proc. Natl. Acad. Sci. U. S. A.",Article,Scopus
"Demir E., Cary M.P., Paley S., Fukuda K., Lemer C., Vastrik I., Wu G., D'Eustachio P., Schaefer C., Luciano J., Schacherer F., Martinez-Flores I., Hu Z., Jimenez-Jacinto V., Joshi-Tope G., Kandasamy K., Lopez-Fuentes A.C., Mi H., Pichler E., Rodchenkov I., Splendiani A., Tkachev S., Zucker J., Gopinath G., Rajasimha H., Ramakrishnan R., Shah I., Syed M., Anwar N., Babur O., Blinov M., Brauner E., Corwin D., Donaldson S., Gibbons F., Goldberg R., Hornbeck P., Luna A., Murray-Rust P., Neumann E., Reubenacker O., Samwald M., Van Iersel M., Wimalaratne S., Allen K., Braun B., Whirl-Carrillo M., Cheung K.-H., Dahlquist K., Finney A., Gillespie M., Glass E., Gong L., Haw R., Honig M., Hubaut O., Kane D., Krupa S., Kutmon M., Leonard J., Marks D., Merberg D., Petri V., Pico A., Ravenscroft D., Ren L., Shah N., Sunshine M., Tang R., Whaley R., Letovksy S., Buetow K.H., Rzhetsky A., Schachter V., Sobral B.S., Dogrusoz U., McWeeney S., Aladjem M., Birney E., Collado-Vides J., Goto S., Hucka M., Le Novere N., Maltsev N., Pandey A., Thomas P., Wingender E., Karp P.D., Sander C., Bader G.D.","The BioPAX community standard for pathway data sharing (Nature Biotechnology (2010) 28, (935-942))",2012,"Nature Biotechnology",30,4,,365,,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84859638634&partnerID=40&md5=c85110b5c90f9d419188b5a91aaaafc2",,"Demir, E.; Cary, M.P.; Paley, S.; Fukuda, K.; Lemer, C.; Vastrik, I.; Wu, G.; D'Eustachio, P.; Schaefer, C.; Luciano, J.; Schacherer, F.; Martinez-Flores, I.; Hu, Z.; Jimenez-Jacinto, V.; Joshi-Tope, G.; Kandasamy, K.; Lopez-Fuentes, A.C.; Mi, H.; Pichler, E.; Rodchenkov, I.; Splendiani, A.; Tkachev, S.; Zucker, J.; Gopinath, G.; Rajasimha, H.; Ramakrishnan, R.; Shah, I.; Syed, M.; Anwar, N.; Babur, Ö.; Blinov, M.; Brauner, E.; Corwin, D.; Donaldson, S.; Gibbons, F.; Goldberg, R.; Hornbeck, P.; Luna, A.; Murray-Rust, P.; Neumann, E.; Reubenacker, O.; Samwald, M.; Van Iersel, M.; Wimalaratne, S.; Allen, K.; Braun, B.; Whirl-Carrillo, M.; Cheung, K.-H.; Dahlquist, K.; Finney, A.; Gillespie, M.; Glass, E.; Gong, L.; Haw, R.; Honig, M.; Hubaut, O.; Kane, D.; Krupa, S.; Kutmon, M.; Leonard, J.; Marks, D.; Merberg, D.; Petri, V.; Pico, A.; Ravenscroft, D.; Ren, L.; Shah, N.; Sunshine, M.; Tang, R.; Whaley, R.; Letovksy, S.; Buetow, K.H.; Rzhetsky, A.; Schachter, V.; Sobral, B.S.; Dogrusoz, U.; McWeeney, S.; Aladjem, M.; Birney, E.; Collado-Vides, J.; Goto, S.; Hucka, M.; Le Novère, N.; Maltsev, N.; Pandey, A.; Thomas, P.; Wingender, E.; Karp, P.D.; Sander, C.; Bader, G.D.",[No abstract available],,"erratum; error; priority journal",,,,,,,"Demir, E.",,,,,,,,10870156,,NABIF,10.1038/nbt0412-365c,,"English","Nat. Biotechnol.",Erratum,Scopus
"Tan C.S.H., Bader G.D.","Phosphorylation sites of higher stoichiometry are more conserved",2012,"Nature Methods",9,4,,317,,,4,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84859165797&partnerID=40&md5=461e7178a3971baca606e2089cddd12b","Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria","Tan, C.S.H., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, Department of Molecular Genetics, University of Toronto, Toronto, Canada, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria; Bader, G.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada, Department of Molecular Genetics, University of Toronto, Toronto, Canada, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada",[No abstract available],,"evolution; follow up; fungus growth; gene mutation; genetic analysis; letter; mass spectrometry; molecular genetics; nonhuman; phylogeny; priority journal; protein phosphorylation; proteomics; Saccharomyces cerevisiae; stoichiometry; Isotope Labeling; Mass Spectrometry; Phosphoric Monoester Hydrolases; Phosphorylation; Proteome",,"Phosphoric Monoester Hydrolases, 3.1.3.-; Proteome",,,,"Wu, R., (2011) Nat Methods, 8, pp. 677-683; Drummond, D.A., Bloom, J.D., Adami, C., Wilke, C.O., Arnold, F.H., (2005) Proc. Natl. Acad. Sci. USA, 102, pp. 14338-14343; Pál, C., Papp, B., Hurst, L.D., (2001) Genetics, 158, pp. 927-931; Ghaemmaghami, S., (2003) Nature, 425, pp. 737-741; Budovskaya, Y.V., Stephan, J.S., Deminoff, S.J., Herman, P.K., (2005) Proc. Natl. Acad. Sci. USA, 102, pp. 13933-13938","Tan, C.S.H.; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; email: ctan@cemm.oeaw.ac.at",,,,,,,,15487091,,,10.1038/nmeth.1941,22453906,"English","Nat. Methods",Letter,Scopus
"Diezmann S., Michaut M., Shapiro R.S., Bader G.D., Cowen L.E.","Mapping the Hsp90 genetic interaction network in candida albicans reveals environmental contingency and rewired circuitry",2012,"PLoS Genetics",8,3, e1002562,,,,8,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84859223051&partnerID=40&md5=bdff15af04585c719236a7e2d923bc98","Department of Molecular Genetics, University of Toronto, Toronto, Canada; The Donnelly Centre, University of Toronto, Toronto, Canada","Diezmann, S., Department of Molecular Genetics, University of Toronto, Toronto, Canada; Michaut, M., The Donnelly Centre, University of Toronto, Toronto, Canada; Shapiro, R.S., Department of Molecular Genetics, University of Toronto, Toronto, Canada; Bader, G.D., The Donnelly Centre, University of Toronto, Toronto, Canada; Cowen, L.E., Department of Molecular Genetics, University of Toronto, Toronto, Canada","The molecular chaperone Hsp90 regulates the folding of diverse signal transducers in all eukaryotes, profoundly affecting cellular circuitry. In fungi, Hsp90 influences development, drug resistance, and evolution. Hsp90 interacts with ~10% of the proteome in the model yeast Saccharomyces cerevisiae, while only two interactions have been identified in Candida albicans, the leading fungal pathogen of humans. Utilizing a chemical genomic approach, we mapped the C. albicans Hsp90 interaction network under diverse stress conditions. The chaperone network is environmentally contingent, and most of the 226 genetic interactors are important for growth only under specific conditions, suggesting that they operate downstream of Hsp90, as with the MAPK Hog1. Few interactors are important for growth in many environments, and these are poised to operate upstream of Hsp90, as with the protein kinase CK2 and the transcription factor Ahr1. We establish environmental contingency in the first chaperone network of a fungal pathogen, novel effectors upstream and downstream of Hsp90, and network rewiring over evolutionary time. © 2012 Diezmann et al.",,"casein kinase II; heat shock protein 90; mitogen activated protein kinase; mitogen activated protein kinase Hog 1; transcription factor; transcription factor Ahr1; unclassified drug; adenosine triphosphate; benzoquinone derivative; geldanamycin; macrocyclic lactam; phosphotransferase; article; Candida albicans; controlled study; downstream processing; environmental contingency; fungal phenomena and functions; fungus growth; gene interaction; gene mapping; genetic interaction network; nonhuman; culture medium; drug effect; gene expression regulation; gene regulatory network; genetics; growth, development and aging; metabolism; microbiology; physiological stress; protein protein interaction; Saccharomyces cerevisiae; signal transduction; Candida albicans; Eukaryota; Fungi; Saccharomyces cerevisiae; Adenosine Triphosphate; Benzoquinones; Candida albicans; Culture Media; Environmental Microbiology; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; HSP90 Heat-Shock Proteins; Lactams, Macrocyclic; Phosphotransferases; Protein Interaction Maps; Saccharomyces cerevisiae; Signal Transduction; Stress, Physiological",,"mitogen activated protein kinase, 142243-02-5; adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; geldanamycin, 30562-34-6; phosphotransferase, 9031-09-8, 9031-44-1; Adenosine Triphosphate, 56-65-5; Benzoquinones; Culture Media; HSP90 Heat-Shock Proteins; Lactams, Macrocyclic; Phosphotransferases, 2.7.-; geldanamycin, 30562-34-6",,,,"Taipale, M., Jarosz, D.F., Lindquist, S., HSP90 at the hub of protein homeostasis: emerging mechanistic insights (2010) Nat Rev Mol Cell Biol, 11, pp. 515-528; Wandinger, S.K., Richter, K., Buchner, J., The Hsp90 chaperone machinery (2008) J Biol Chem, 283, pp. 18473-18477; Trepel, J., Mollapour, M., Giaccone, G., Neckers, L., Targeting the dynamic HSP90 complex in cancer (2010) Nat Rev Cancer, 10, pp. 537-549; 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E.; Department of Molecular Genetics, University of Toronto, Toronto, Canada; email: leah.cowen@utoronto.ca",,,,,,,,15537390,,,10.1371/journal.pgen.1002562,,"English","PLoS Genet.",Article,Scopus
"Kim T., Tyndel M.S., Huang H., Sidhu S.S., Bader G.D., Gfeller D., Kim P.M.","MUSI: An integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets",2012,"Nucleic Acids Research",40,6,,,,,6,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84859303311&partnerID=40&md5=f41da226d0ddd7a801ef0aa1f6426ce7","Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada; Edward S. Rogers Sr Department of Electrical and Computer Engineering, University of Toronto, ON M5S 3G4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A4, Canada; Swiss Institute of Bioinformatics, Molecular Modeling, Génopode, CH-1015 Lausanne, Switzerland","Kim, T., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada; Tyndel, M.S., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Edward S. Rogers Sr Department of Electrical and Computer Engineering, University of Toronto, ON M5S 3G4, Canada; Huang, H., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A4, Canada; Sidhu, S.S., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A4, Canada; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A4, Canada; Gfeller, D., Swiss Institute of Bioinformatics, Molecular Modeling, Génopode, CH-1015 Lausanne, Switzerland; Kim, P.M., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A4, Canada","Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors. © 2011 The Author(s).",,"protein SH3; RNA binding protein; transcription factor; article; binding affinity; binding site; computer program; controlled study; DNA sequence; genetic algorithm; human; microarray analysis; mouse; nonhuman; nucleic acid analysis; nucleotide sequence; peptide analysis; prediction; priority journal; protein binding; protein DNA interaction; protein domain; protein protein interaction; sensitivity and specificity; sequence alignment; sequence analysis; Animals; Binding Sites; High-Throughput Nucleotide Sequencing; Humans; Ligands; Mice; Peptide Library; Peptides; Position-Specific Scoring Matrices; Protein Interaction Domains and Motifs; Sequence Analysis, Protein; Software; src Homology Domains; Transcription Factors",,"Ligands; Peptide Library; Peptides; Transcription Factors","MUltiple Specificity Identifier",,,"Pawson, T., Nash, P., Assembly of cell regulatory systems through protein interaction domains (2003) Science, 300 (5618), pp. 445-452. , DOI 10.1126/science.1083653; Mitchell, P.J., Tjian, R., Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins (1989) Science, 245 (4916), pp. 371-378; Hutti, J.E., Jarrell, E.T., Chang, J.D., Abbott, D.W., Storz, P., Toker, A., Cantley, L.C., Turk, B.E., A rapid method for determining protein kinase phosphorylation specificity (2004) Nat. 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"le Novere N., Hucka M., Anwar N., Bader G.D., Demir E., Moodie S., Sorokin A.","Meeting report from the first meetings of the Computational Modeling in Biology Network (COMBINE)",2011,"Standards in Genomic Sciences",5,2,,230,242,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-83255181846&partnerID=40&md5=23b05695a042b6fdc8d8d9aa2d3ba3c6","EMBL-EBI, Hinxton, CB10 1SD, United Kingdom; Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, United States; General Bioinformatics Limited, Reading, United Kingdom; The Donnelly Centre, University of Toronto, Toronto, ON M5S, Canada; MSKCC - Computational Biology Center, New York, NY, United States; Eight Pillars Ltd, 19 Redford Walk, Edinburgh, United Kingdom; School of Informatics, University of Edinburgh, Edinburgh, United Kingdom","le Novère, N., EMBL-EBI, Hinxton, CB10 1SD, United Kingdom; Hucka, M., Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, United States; Anwar, N., General Bioinformatics Limited, Reading, United Kingdom; Bader, G.D., The Donnelly Centre, University of Toronto, Toronto, ON M5S, Canada; Demir, E., MSKCC - Computational Biology Center, New York, NY, United States; Moodie, S., Eight Pillars Ltd, 19 Redford Walk, Edinburgh, United Kingdom; Sorokin, A., School of Informatics, University of Edinburgh, Edinburgh, United Kingdom","The Computational Modeling in Biology Network (COMBINE), is an initiative to coordinate the development of the various community standards and formats in computational systems biology and related fields. This report summarizes the activities pursued at the first annual COMBINE meeting held in Edinburgh on October 6-9 2010 and the first HARMONY hackathon, held in New York on April 18-22 2011. The first of those meetings hosted 81 attendees. Discussions covered both official COMBINE standards-(BioPAX, SBGN and SBML), as well as emerging efforts and interoperability between different formats. The second meeting, oriented towards software developers, welcomed 59 participants and witnessed many technical discussions, development of improved standards support in community software systems and conversion between the standards. Both meetings were resounding successes and showed that the field is now mature enough to develop representation formats and related standards in a coordinated manner.",,,,,,,,"Hucka, M., Bolouri, H., Finney, A., Sauro, H.M., Doyle, J.C., Kitano, H., Arkin, A.P., Cornish-Bowden, A., The Systems Biology Markup Language (SBML): A medium for representation and exchange of biochemical network models (2003) Bioinformatics, 19, pp. 524-531. , PubMed doi:10.1093/bioinformatics/btg015; Demir, E., Cary, M.P., Paley, S., Fukuda, K., Lemer, C., Vastrik, I., Wu, G., Luciano, J., BioPAX-A community standard for pathway data sharing (2010) Nat Biotechnol, 28, pp. 935-942. , PubMed doi:10.1038/nbt.1666; le Novère, N., Hucka, M., Mi, H., Moodie, S., Shreiber, F., Sorokin, A., Demir, E., Wimalaratne, S., The Systems Biology Graphical Notation (2009) Nat Biotechnol, 27, pp. 735-741. , PubMed doi:10.1038/nbt.1558; le Novère, N., Courtot, M., Laibe, C., Adding semantics in kinetics models of biochemical pathways (2007) Proc 2nd Intl Symp Exp Std Cond Enz Charact, pp. 137-153. , http://www.beilstein-institut.de/index.php?id=196, Available at; Lloyd, C.M., Halstead, M.D., Nielsen, P.F., CellML, its future, present and past (2004) Prog Biophys Mol Biol, 85, pp. 433-450. , PubMed doi:10.1016/j.pbiomolbio.2004.01.004; Gleeson, P., Crook, S., Cannon, R.C., Hines, M.L., Billings, G.O., Farinella, M., Morse, T.M., Bhalla, U.S., NeuroML: A language for describing data driven models of neurons and networks with a high degree of biological detail (2010) PLOS Comput Biol, 6, pp. e1000815. , PubMed doi:10.1371/journal.pcbi.1000815; Köhn, D., le Novère, N., SED-ML-An XML Format for the implementation of the MIASE guidelines (2008) Lect Notes Bioinfo, 5307, pp. 176-190; COMBINE, , http://co.mbine.org; Chandran, D., Bergmann, F.T., Sauro, H.M., TinkerCell: Modular CAD tool for synthetic biology (2009) J Biol Eng, 3, p. 19. , PubMed doi:10.1186/1754-1611-3-19; Cell ML, , http://www.cellml.org; Field ML, , http://www.Physiome.org.nz/xml_languages/fieldml; Hunter, P., (2010) The Physiome languages: CellML and FieldML, , www.physiome.org.nz/xml_languages/fieldml, Available from Nat Preced; Physiome Model Repository, , http://www.cellml.org/tools/pmr; Nielsen, P., (2010) CellML 1.1 modularity, , Available from Nat Preced; OpenCell, , http://www.cellml.org/tools/opencell; Garny, A., (2010) OpenCell-Status and plans, , Available from Nat Preced; Simulation Experiment Description Markup Language (SED-ML), , http://sed-ml.org; API library libSedML, , http://libsedml.sourceforge.net/libSedML/Welcome.html; Bergmann, F., (2011) The Simulation Experiment Description Markup Language, , Update. Available from Nat Preced; Java API library JlibSEDML, , http://sourceforge.net/projects/jlibsedml; SBSI, , http://www.sbsi.ed.ac.uk; Adams, R., Moraru, I., Lakshminaryana, A., (2010) jlibSEDML-a Java library for working with SED-ML, , Available from Nat Preced; Systems Biology Graphical Notation (SBGN), , http://www.sbgn.org; le Novère, N., (2010) Report on the status of SBGN ER and proposed extensions, , Available from Nat Preced; Moodie, S., (2011) SBGN-PD: Current status, future changes and unresolved issues, , Available from Nat Preced; Mi, H., (2011) SBGN Activity Flow Update, , Available from Nat Preced; The software system SBGN-ED, , http://vanted.ipk-gatersleben.de/addons/sbgn-ed/; Arcadia, , http://arcadiapathways.sourceforge.net; VISIBIOweb, , http://www.bilkent.edu.tr/~bcbi/pvs.html; LibSBGN, a Java API for manipulating SBGN, , http://libsbgn.sf.net; Villeger, A., LibSBGN: Current status and future plans, , Available from Nat Preced 2010; Visualization and Analysis of Networks containing Experimental Data, , http://vanted.ipk-gatersleben.de; Jovanovska, D., Fages, F., Soliman, S., (2010) SBGN support in BIOCHAM, , Available from Nat Preced; The Biochemical Abstract Machine, , http://inria.fr/BIOCHAM; Gauges, R., (2010) SBML layout and render news, , Available from Nat Preced, contraintes; BioPAX in CellDesigner, , http://www.celldesigner.org; Muruganujan, A., Mi, H., (2011) BioPAX Support in CellDesigner, , Available from Nat Preced; BioUML, , http://www.biouml.org; Proteomics Standards Initiative (PSI), , http://www.psidev.info; iMEX collaboration, , http://www.imexconsortium.org; Golebiewski, M., (2010) Exchanging Experimental Kinetic Data via SabioML, , Available from Nat Preced; Commons, P., http://www.pathwaycommons.orgCerami, E.G., Gross, B.E., Demir, E., Rodchenkov, I., Babur, O., Anwar, N., Schultz, N., Sander, C., Pathway Commons, a web resource for biological pathway data (2011) Nucleic Acids Res, 39, pp. D685-D690. , PubMed doi:10.1093/nar/gkq1039; BioPAX, , http://www.biopax.org; Reactome pathway database, , http://www.reactome.org; Systems Biology Ontology (SBO), , http://biomodels.net/sbo; Juty, N., (2010) Systems Biology Ontology: Update, , Available from Nat Preced; Resources MIRIAM, , http://www.ebi.ac.uk/miriam; Laibe, C., (2010) MIRIAM Resources: Next steps, , Available from Nat Preced; Splendiani, A., (2010) BioPAX: Next steps for Semantic Web / CV workgroup, , Available from Nat Preced; Swainston, N., (2010) The SBML Level 3 Annotation package: An initial proposal, , Available from Nat Preced; Henkel, R., Endler, L., le Novère, N., Peters, A., Waltemath, D., Ranked Retrieval of Computational Biology Models (2010) BMC Bioinformatics, 11, p. 423. , PubMed; Semantic SBML, , http://www.semanticsbml.org; Liebermeister, W., Krause, F., Schulz, M., Lubitz, T., (2010) SemanticSBML-state of affairs, , Available from Nat Preced; Schulz, M., Krause, F., le Novère, N., Klipp, E., Liebermeister, W., Retrieval, alignment, and clustering of computational models based on semantic annotations (2011) Mol Syst Biol, 7, p. 512. , PubMed doi:10.1038/msb.2011.41; PathVision 9 pathway vizualization tool, , http://www.pathvisio.org/; van Iersel, M.P., Kelder, T., Pico, A.R., Hanspers, K., Coort, S., Conklin, B.R., Evelo, C., Presenting and exploring biological pathways with PathVisio (2008) BMC Bioinformatics, 9, p. 399. , PubMed doi:10.1186/1471-2105-9-399; WikiPathways, , http://www.wikipathways.org; Pico, A.R., Kelder, T., van Iersel, M.P., Hanspers, K., Conklin, B.R., Evelo, C., WikiPathways: Pathway editing for the people (2008) PLoS Biol, 6, pp. e184. , PubMed doi:10.1371/journal.pbio.0060184; Systems Biology Format Converter (SBFC), , http://sbfc.sourceforge.net; Smith, L., (2010) Tales from the code front: Translating Modularity, , Available from Nat Preced; Laibe, C., Hoehl, M., (2010) BioModels Database: Next generation model repository, , Available from Nat Preced; BioModels Database, , http://www.ebi.ac.uk/biomodels; Li, C., Donizelli, M., Rodriguez, N., Dharuri, H., Endler, L., Chelliah, V., Li, L., Stefan, M.I., BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models (2010) BMC Syst Biol, 4, p. 92. , PubMed doi:10.1186/1752-0509-4-92; Common Query Interface PSI. (PSICQUIC), , http://code.google.com/p/psicquic; Hermjakob, H., Montecchi-Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., Ceol, A., Moore, S., von Mering, C., The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data (2004) Nat Biotechnol, 22, pp. 177-183. , PubMed doi:10.1038/nbt926; Kohn, K.W., Aladjem, M.I., Weinstein, J.N., Pommier, Y., Molecular interaction maps of bioregulatory networks: A general rubric for systems biology (2005) Mol Biol Cell, 17, pp. 1-13. , PubMed doi:10.1091/mbc.E05-09-0824; Zinovyev, A., (2010) BiNoM Cytoscape Plugin for constructing, querying and analyzing biological networks, using systems biology standards, , Available from Nat Preced; BiNoM, , http://bioinfo-out.curie.fr/projects/binom; le Novère, N., (2011) COMBINE-a vision, , Available from Nat Preced; Neuro ML, , http://www.neuroml.org; Cannon, R., (2010) Types, models and instances: A perspective from neuroscience, , Available from Nat Preced; Mazein, A., (2010) Metabolic Network Representation in SBGN PD: EC and Identity Gate, , Available from Nat Preced; Muetzelfeldt, R., (2010) A generic approach for representing complex structures in biological models, , Available from Nat Preced; SBML, , http://sbml.org; Hucka, M., (2010) SBML Level 3 Brief Update, , Available from Nat Preced doi:10.1038/npre.2010.5011.2; Olivier, B., Bergmann, F., (2010) Progress report: SBML Level 3 package FBA, , Available from Nat Preced; Smith, L., Hucka, M., (2010) SBML Level 3 Hierarchical Model Composition, , Available from Nat Preced; Keating, S., (2010) Update on libSBML status, , Available from Nat Preced; ibSBML, , http://sbml.org/Software/libSBML; Rodriguez, N., Dräger, A., (2010) JSBML, , Available from Nat Preced; Java SBML API library, , http://sbml.org/Software/JSBML; Myers, C., (2010) Implementation of SBML Level 3 Support within iBioSim, , Available from Nat Preced; Myers, C.J., Barker, N., Jones, K., Kuwahara, H., Madsen, C., Nguyen, N.P., iBioSim: A tool for the analysis and design of genetic circuits (2009) Bioinformatics, 25, pp. 2848-2849. , PubMed doi:10.1093/bioinformatics/btp457; iBioSim, , http://www.async.ece.utah.edu/iBioSim; Dräger, A., Nitschmann, S., Dörr, A., Eichner, J., Ziller, M., Zell, A., (2010) Context-based generation of kinetic equations with SBMLsqueezer 1.3, , Available from Nat Preced doi:10.1038/npre.2010.4983.1; SBMLsqueezer, , http://www.ra.cs.uni-tuebingen.de/software/SBMLsqueezer; Crdata, , http://crdata.org; SBOL, , http://www.sbolstandard.org; Sloan-Kettering Cancer Center, , http://co.mbine.org/events/HARMONY_2011; SBGN-PD, , http://www.sbgn.org/Discussion_on_Issues; Activity flow, , http://www.sbgn.org/AF_node; Chibe Visualization tool, , http://www.bilkent.edu.tr/~bcbi/chibe.html; KEGG pathways to SBML, , http://www.ra.cs.uni-tuebingen.de/software/KEGGtranslator; Kinetic SAO, , http://www.biomodels.net/kisao; The 12 th ICSB at the Heidelberg Institute for Theoretical Studies, , http://co.mbine.org/events/COMBINE_2011","le Novère, N.; EMBL-EBI, Hinxton, CB10 1SD, United Kingdom; email: lenov@ebi.ac.uk",,,,,,,,19443277,,,10.4056/sigs.2034671,,"English","Stand. Genomic Sci.",Article,Scopus
"Raju R., Balakrishnan L., Nanjappa V., Bhattacharjee M., Getnet D., Muthusamy B., Thomas J.K., Sharma J., Rahiman B.A., Harsha H.C., Shankar S., Prasad T.S.K., Mohan S.S., Bader G.D., Wani M.R., Pandey A.","A comprehensive manually curated reaction map of RANKL/RANK-signaling pathway",2011,"Database",2011,, bar021,,,,4,"http://www.scopus.com/inward/record.url?eid=2-s2.0-80052901014&partnerID=40&md5=848d02c998b5577f49667b79c92cd2b1","Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Department of Biotechnology, Kuvempu University, Shankaraghatta 577451, India; School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India; National Center for Cell Science, University of Pune Campus, Pune 411007, India; Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry 605 014, India; Manipal University, Madhav Nagar, Manipal-576104, India; Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India; Research Unit for Immunoinformatics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan; Banting and Best Department of Medical, Research and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5S 3E1, Canada; McKusick-Nathans Institute of Genetic Medicine, United States; Department of Biological Chemistry, United States; Department of Pathology, United States; Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States","Raju, R., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankaraghatta 577451, India; Balakrishnan, L., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankaraghatta 577451, India; Nanjappa, V., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Bhattacharjee, M., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India; Getnet, D., National Center for Cell Science, University of Pune Campus, Pune 411007, India; Muthusamy, B., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry 605 014, India; Thomas, J.K., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Sharma, J., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Manipal University, Madhav Nagar, Manipal-576104, India; Rahiman, B.A., Department of Biotechnology, Kuvempu University, Shankaraghatta 577451, India; Harsha, H.C., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Shankar, S., Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India; Prasad, T.S.K., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Bioinformatics Centre, School of Life Sciences, Pondicherry University, Puducherry 605 014, India; Mohan, S.S., Institute of Bioinformatics, International Technology Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankaraghatta 577451, India, Research Unit for Immunoinformatics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan; Bader, G.D., Banting and Best Department of Medical, Research and Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5S 3E1, Canada; Wani, M.R., National Center for Cell Science, University of Pune Campus, Pune 411007, India; Pandey, A., McKusick-Nathans Institute of Genetic Medicine, United States, Department of Biological Chemistry, United States, Department of Pathology, United States, Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States","Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor necrosis factor (TNF) superfamily that plays a key role in the regulation of differentiation, activation and survival of osteoclasts and also in tumor cell migration and bone metastasis. Osteoclast activation induced by RANKL regulates hematopoietic stem cell mobilization as part of homeostasis and host defense mechanisms thereby linking regulation of hematopoiesis with bone remodeling. Binding of RANKL to its receptor, Receptor activator of nuclear factor-kappa B (RANK) activates molecules such as NF-kappa B, mitogen activated protein kinase (MAPK), nuclear factor of activated T cells (NFAT) and phosphatidyl 3-kinase (PI3K). Although the molecular and cellular roles of these molecules have been reported previously, a systematic cataloging of the molecular events induced by RANKL/RANK interaction has not been attempted. Here, we present a comprehensive reaction map of the RANKL/RANK-signaling pathway based on an extensive manual curation of the published literature. We hope that the curated RANKL/RANK-signaling pathway model would enable new biomedical discoveries, which can provide novel insights into disease processes and development of novel therapeutic interventions. © The Author(s) 2011.",,"osteoclast differentiation factor; receptor activator of nuclear factor kappa B; TNFRSF11A protein, human; TNFSF11 protein, human; article; data base; factual database; genetics; human; metabolism; signal transduction; Database Management Systems; Databases, Factual; Humans; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction",,"osteoclast differentiation factor, 200145-93-3; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; TNFRSF11A protein, human; TNFSF11 protein, human",,,,"Collin-Osdoby, P., Rothe, L., Anderson, F., Receptor activator of nf-kappa b and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis (2001) J. Biol. 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"Raju R., Nanjappa V., Balakrishnan L., Radhakrishnan A., Thomas J.K., Sharma J., Tian M., Palapetta S.M., Subbannayya T., Sekhar N.R., Muthusamy B., Goel R., Subbannayya Y., Telikicherla D., Bhattacharjee M., Pinto S.M., Syed N., Srikanth M.S., Sathe G.J., Ahmad S., Chavan S.N., Kumar G.S.S., Marimuthu A., Prasad T.S.K., Harsha H.C., Rahiman B.A., Ohara O., Bader G.D., Mohan S.S., Schiemann W.P., Pandey A.","NetSlim: High-confidence curated signaling maps",2011,"Database",2011,, bar032,,,,2,"http://www.scopus.com/inward/record.url?eid=2-s2.0-84864041694&partnerID=40&md5=6c45afb0f5b7bda46b80290e28f80942","Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United States; Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Rajiv Gandhi University of Health Sciences, Bangalore 560041, Karnataka, India; School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690 525, India; Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 2300045, Japan; Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada; Research Unit for Immunoinformatics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 2300045, Japan; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States; Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States; Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States; Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States","Raju, R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Nanjappa, V., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Balakrishnan, L., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Radhakrishnan, A., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Thomas, J.K., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Sharma, J., Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India; Tian, M., Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United States; Palapetta, S.M., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Subbannayya, T., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Sekhar, N.R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Muthusamy, B., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Goel, R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Subbannayya, Y., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Rajiv Gandhi University of Health Sciences, Bangalore 560041, Karnataka, India; Telikicherla, D., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Bhattacharjee, M., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690 525, India; Pinto, S.M., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India; Syed, N., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Srikanth, M.S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Sathe, G.J., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Ahmad, S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Chavan, S.N., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Kumar, G.S.S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Marimuthu, A., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India; Prasad, T.S.K., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India; Harsha, H.C., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Rahiman, B.A., Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India; Ohara, O., Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 2300045, Japan; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada; Mohan, S.S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology, Kuvempu University, Shankarghatta 577451, India, Research Unit for Immunoinformatics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 2300045, Japan; Schiemann, W.P., Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, United States; Pandey, A., McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States, Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States, Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States, Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore 21205, MD, United States","We previously developed NetPath as a resource for comprehensive manually curated signal transduction pathways. 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"Morris J.H., Apeltsin L., Newman A.M., Baumbach J., Wittkop T., Su G., Bader G.D., Ferrin T.E.","ClusterMaker: A multi-algorithm clustering plugin for Cytoscape",2011,"BMC Bioinformatics",12,, 436,,,,14,"http://www.scopus.com/inward/record.url?eid=2-s2.0-80655132169&partnerID=40&md5=30b32c8c6d3e77d78335c13f1107fd38","Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, United States; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, United States; Max Planck Institute for Informatics, Saarbrücken, Germany; Buck Institute for Age Research, Novato, CA, United States; Bioinformatics Program, University of Michigan, Ann Arbor, MI, United States; National Center for Integrative Biomedical Informatics, University of Michigan, Ann Arbor, MI, United States; The Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Ontario, Canada; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, United States","Morris, J.H., Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, United States; Apeltsin, L., Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, United States; Newman, A.M., Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, United States; Baumbach, J., Max Planck Institute for Informatics, Saarbrücken, Germany; Wittkop, T., Buck Institute for Age Research, Novato, CA, United States; Su, G., Bioinformatics Program, University of Michigan, Ann Arbor, MI, United States, National Center for Integrative Biomedical Informatics, University of Michigan, Ann Arbor, MI, United States; Bader, G.D., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Ontario, Canada; Ferrin, T.E., Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, United States, Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, United States","Background: In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present clusterMaker, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. clusterMaker is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view), k-means, k-medoid, SCPS, AutoSOME, and native (Java) MCL.Results: Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast Saccharomyces cerevisiae; and the cluster analysis of the vicinal oxygen chelate (VOC) enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section.Conclusions: The Cytoscape plugin clusterMaker provides a number of clustering algorithms and visualizations that can be used independently or in combination for analysis and visualization of biological data sets, and for confirming or generating hypotheses about biological function. Several of these visualizations and algorithms are only available to Cytoscape users through the clusterMaker plugin. clusterMaker is available via the Cytoscape plugin manager. © 2011 Morris et al; licensee BioMed Central Ltd.",,"Saccharomyces cerevisiae; isomerase; methylmalonyl coenzyme a racemase; methylmalonyl-coenzyme A racemase; algorithm; animal; article; cluster analysis; computer program; enzymology; genetics; genomics; mouse; protein protein interaction; Saccharomyces cerevisiae; Algorithms; Animals; Cluster Analysis; Genomics; Mice; Protein Interaction Maps; Racemases and Epimerases; Saccharomyces cerevisiae; Software",,"isomerase, 9013-19-8; methylmalonyl coenzyme a racemase, 9024-03-7; Racemases and Epimerases, 5.1.-; methylmalonyl-coenzyme A racemase, 5.1.99.1",,,,"Eisen, M.B., Spellman, P.T., Brown, P.O., Botstein, D., Cluster analysis and display of genome-wide expression patterns (1998) Proc Natl Acad Sci USA, 95 (25), pp. 14863-14868. , 10.1073/pnas.95.25.14863, 24541, 9843981; 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"Wallace I.M., Urbanus M.L., Luciani G.M., Burns A.R., Han M.K.L., Wang H., Arora K., Heisler L.E., Proctor M., St. Onge R.P., Roemer T., Roy P.J., Cummins C.L., Bader G.D., Nislow C., Giaever G.","Compound prioritization methods increase rates of chemical probe discovery in model organisms",2011,"Chemistry and Biology",18,10,,1273,1283,,7,"http://www.scopus.com/inward/record.url?eid=2-s2.0-80055075327&partnerID=40&md5=2b4009727ba1fe7f1d445932c7588df4","Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada; Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Infectious Disease Research, Merck, Kenilworth, NJ 07033, United States; Stanford Genome Technology Center, Palo Alto, CA 94304, United States","Wallace, I.M., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada; Urbanus, M.L., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada; Luciani, G.M., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Burns, A.R., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Han, M.K.L., Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada; Wang, H., Infectious Disease Research, Merck, Kenilworth, NJ 07033, United States; Arora, K., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Heisler, L.E., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada; Proctor, M., Stanford Genome Technology Center, Palo Alto, CA 94304, United States; St. Onge, R.P., Stanford Genome Technology Center, Palo Alto, CA 94304, United States; Roemer, T., Infectious Disease Research, Merck, Kenilworth, NJ 07033, United States; Roy, P.J., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Cummins, C.L., Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada; Bader, G.D., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Nislow, C., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Giaever, G., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada","Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ∼81,000 compounds in Saccharomyces cerevisiae and identified ∼7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ∼7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided. © 2011 Elsevier Ltd All rights reserved.",,"acyl coenzyme A desaturase; benzofuran derivative; delta 9 fatty acid desaturase; delta-9 fatty acid desaturase; enzyme inhibitor; ERG7.153; lanosterol synthase; mutase; piperazine derivative; article; Bacillus subtilis; Bayes theorem; biological model; Candida albicans; chemistry; computer simulation; drug antagonism; drug effect; Escherichia coli; growth, development and aging; HeLa cell; human; metabolism; molecular library; phenotype; Saccharomyces cerevisiae; Bacillus subtilis; Bayes Theorem; Benzofurans; Candida albicans; Computer Simulation; Enzyme Inhibitors; Escherichia coli; Fatty Acid Desaturases; HeLa Cells; Humans; Intramolecular Transferases; Models, Biological; Phenotype; Piperazines; Saccharomyces cerevisiae; Small Molecule Libraries; Saccharomyces cerevisiae",,"acyl coenzyme A desaturase, 9014-34-0; lanosterol synthase, 9032-71-7; mutase, 9047-56-7; Benzofurans; ERG7.153; Enzyme Inhibitors; Fatty Acid Desaturases, 1.14.19.-; Intramolecular Transferases, 5.4.-; Piperazines; Small Molecule Libraries; delta-9 fatty acid desaturase, 1.14.99.-; lanosterol synthase, 5.4.99.7",,,,"Agresti, J.J., Antipov, E., Abate, A.R., Ahn, K., Rowat, A.C., Baret, J.-C., Marquez, M., Weitz, D.A., Ultrahigh-throughput screening in drop-based microfluidics for directed evolution (2010) Proc. 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Sci., 29, pp. 163-172; Voyron, S., Rocco, F., Ceruti, M., Forni, P., Pla, A.F., Sarpietro, M.G., Varese, G.C., Marchisio, V.F., Antifungal activity of bis-azasqualenes, inhibitors of oxidosqualene cyclase (2010) Mycoses, 53, pp. 481-487; Wang, Y., Bolton, E., Dracheva, S., Karapetyan, K., Shoemaker, B.A., Suzek, T.O., Wang, J., Bryant, S.H., An overview of the PubChem BioAssay resource (2010) Nucleic Acids Res., 38 (DATABASE ISSUE), pp. D255-D266; Wheeler, G.N., Brändli, A.W., Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus (2009) Dev. Dyn., 238, pp. 1287-1308; Workman, P., Collins, I., Probing the probes: Fitness factors for small molecule tools (2010) Chem. Biol., 17, pp. 561-577; Xu, D., Jiang, B., Ketela, T., Lemieux, S., Veillette, K., Martel, N., Davison, J., Bachewich, C., Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans (2007) PLoS Pathog., 3, p. 92; Xu, D., Sillaots, S., Davison, J., Hu, W., Jiang, B., Kauffman, S., Martel, N., Trosok, S., Chemical genetic profiling and characterization of small-molecule compounds that affect the biosynthesis of unsaturated fatty acids in Candida albicans (2009) J. Biol. Chem., 284, pp. 19754-19764; Yan, Z., Costanzo, M., Heisler, L.E., Paw, J., Kaper, F., Andrews, B.J., Boone, C., Nislow, C., Yeast Barcoders: A chemogenomic application of a universal donor-strain collection carrying bar-code identifiers (2008) Nat. Methods, 5, pp. 719-725","Giaever, G.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; email: g.giaever@utoronto.ca",,,,,,,,10745521,,CBOLE,10.1016/j.chembiol.2011.07.018,22035796,"English","Chem. Biol.",Article,Scopus
"Wallace I.M., Bader G.D., Giaever G., Nislow C.","Displaying chemical information on a biological network using cytoscape",2011,"Methods in Molecular Biology",781,,,363,376,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-80054741187&partnerID=40&md5=418638a84dcb9a912611f45142bc778b","Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Banting and Best Department of Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada","Wallace, I.M., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Bader, G.D., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada; Giaever, G., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Nislow, C., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada","Cytoscape is an open-source software package that is widely used to integrate and visualize diverse data sets in biology. This chapter explains how to use Cytoscape to integrate open-source chemical information with a biological network. By visualizing information about known compound-target interactions in the context of a biological network of interest, one can rapidly identify novel avenues to perturb the system with compounds and, for example, potentially identify therapeutically relevant targets. Herein, two different protocols are explained in detail, with no prior knowledge of Cytoscape assumed, which demonstrate how to incorporate data from the ChEMBL database with either a gene-gene or a protein-protein interaction network. ChEMBL is a very large, open-source repository of compound-target information available from the European Molecular Biology Laboratory. © 2011 Springer Science+Business Media, LLC.","Chemical biological networks; Chemical networks; Cytoscape; Druggable targets; Network visualization","article; biology; computer program; drug effect; gene regulatory network; genetic database; methodology; molecularly targeted therapy; protein database; protein protein interaction; Computational Biology; Databases, Genetic; Databases, Protein; Gene Regulatory Networks; Molecular Targeted Therapy; Protein Interaction Maps; Software",,,,,,"Shannon, P., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13 (11), pp. 2498-2504; Merico, D., Gfeller, D., Gd, B., How to visually interpret biological data using networks (2009) Nat Biotechnol, 27 (10), pp. 921-924; Cline, M.S., Integration of biological networks and gene expression data using Cytoscape (2007) Nature Protocols, 2 (10), pp. 2366-2382; Costanzo, M., The genetic landscape of a cell (2010) Science, 327 (5964), pp. 425-431; Audeh, M.W., Oral poly (ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: A proof-of-concept trial (2010) Lancet, 376 (9737), pp. 245-251; Wishart, D.S., DrugBank: A comprehensive resource for in silico drug discovery and exploration (2006) Nucleic Acids Research, 34, pp. D668-D672. , Database issue; Kuhn, M., STITCH: Interaction networks of chemicals and proteins (2008) Nucleic Acids Res, 36 (DATABASE ISSUE), pp. D684-D688; Montojo, J., GeneMANIA cytoscape plugin: Fast gene function predictions on the desktop (2010) Bioinformatics; Ferro, A., NetMatch: A Cytoscape plugin for searching biological networks (2007) Bioinformatics, 23 (7), pp. 910-912; Cytoscape Home Page, , http://www.Cytoscape.org; ChemViz Plugin Home Page, , http://www.cgl.ucsf.edu/Cytoscape/chemViz; Supplementary Web Page, , http://baderlab.org/VisualizingChemicalInformation; Barbie, D.A., Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 (2009) Nature, 462 (7269), pp. 108-112; Luo, J., A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene (2009) Cell, 137 (5), pp. 835-848; Irwin, J.J., Bk, S., ZINC-a free database of commercially available compounds for virtual screening (2005) Journal of Chemical Information and Modeling, 45 (1), pp. 177-182; Zhu, F., Update of TTD: Therapeutic target database (2010) Nucleic Acids Research, 38 (DATABASE ISSUE), pp. D787-D791; Orchard, S., Implementing data standards: A report on the HUPOPSI workshop September 2009, Toronto, Canada (2010) Proteomics, 10 (10), pp. 1895-1898; Ceol, A., MINT, the molecular interaction database: 2009 update (2010) Nucleic Acids Res, 38 (DATABASE ISSUE), pp. D532-D539; PSICQUIC Databases, , http://www.ebi.ac.uk/Tools/webservices/psicquic/registry/registry?action= STATUS; Liang, D.-C., K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements (2006) Cancer, 106 (4), pp. 950-956; Han, L., Wang, Y., Sh, B., A survey of across-target bioactivity results of small molecules in PubChem (2009) Bioinformatics, 25 (17), pp. 2251-2255; UniProt, , www.uniprot.org; Côté, R.G., The Protein Identifier Cross-Referencing (PICR) service: Reconciling protein identifiers across multiple source databases (2007) BMC Bioinformatics, 8, p. 401","Nislow, C.; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; email: corey.nislow@utoronto.ca","Cagney G.Emili A.",,,,,,,10643745,9781617792755,,10.1007/978-1-61779-276-2_18,21877291,"English","Methods Mol. Biol.",Article,Scopus
"Merico D., Isserlin R., Bader G.D.","Visualizing gene-set enrichment results using the cytoscape plug-in enrichment map",2011,"Methods in Molecular Biology",781,,,257,277,,1,"http://www.scopus.com/inward/record.url?eid=2-s2.0-80054761009&partnerID=40&md5=5dc2e93ae657d34c3c7987f2b756ba7c","Banting and Best Department, Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada","Merico, D., Banting and Best Department, Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Isserlin, R., Banting and Best Department, Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bader, G.D., Banting and Best Department, Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada","Gene-set enrichment analysis finds functionally coherent gene-sets, such as pathways, that are statistically overrepresented in a given gene list. Ideally, the number of resulting sets is smaller than the number of genes in the list, thus simplifying interpretation. However, the increasing number and redundancy of -gene-sets used by many current enrichment analysis resources work against this ideal. ""Enrichment Map"" is a Cytoscape plug-in that helps overcome gene-set redundancy and aids in the interpretation of enrichment results. Gene-sets are organized in a network, where each set is a node and links represent gene overlap between sets. Automated network layout groups related gene-sets into -network clusters, enabling the user to quickly identify the major enriched functional themes and more easily interpret enrichment results. © 2011 Springer Science+Business Media, LLC.","Functional enrichment; Gene ontology; Gene-set enrichment; Microarray data analysis; Pathways","article; biology; computer program; gene regulatory network; genetic database; methodology; Computational Biology; Databases, Genetic; Gene Regulatory Networks; Software",,,,,,"Allison, D.B., Cui, X., Page, G.P., Sabripour, M., Microarray data analysis: From disarray to consolidation and consensus (2006) Nature Reviews Genetics, 7, pp. 55-65; Da Huang, W., Sherman, B.T., Tan, Q., Collins, J.R., Alvord, W.G., Roayaei, J., Stephens, R., Lempicki, R.A., The DAVID Gene Functional Classification Tool: A novel biological module-centric algorithm to functionally analyze large gene lists (2007) Genome Biol, 8, pp. R183; Da, H.W., Sherman, B.T., Lempicki, R.A., Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources (2009) Nat Protoc, 4, pp. 44-57; Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Mesirov, J.P., Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles (2005) Proceedings of the National Academy of Sciences of the United States of America, 102, pp. 15545-15550; Isserlin, R., Merico, D., Alikhani-Koupaei, R., Gramolini, A., Bader, G.D., Emili, A., Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps (2010) Proteomics, pp. 1316-1327; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504; Cline, M.S., Smoot, M., Cerami, E., Kuchinsky, A., Landys, N., Workman, C., Christmas, R., Bader, G.D., Integration of biological networks and gene expression data using Cytoscape (2007) Nature Protocols, 2, pp. 2366-2382; Lin, C.-Y., Vega, V.B., Thomsen, J.S., Zhang, T., Kong, S.L., Xie, M., Chiu, K.P., Liu, E.T., Whole-genome cartography of estrogen receptor alpha binding sites (2007) PLoS Genetics, 3, pp. e87","Bader, G.D.; Banting and Best Department, Medical Research, Centre for Cellular and Biomolecular Research (CCBR), Toronto, ON, Canada; email: gary.bader@utoronto.ca","Cagney G.Emili A.",,,,,,,10643745,9781617792755,,10.1007/978-1-61779-276-2_12,21877285,"English","Methods Mol. Biol.",Article,Scopus
"Aranda B., Blankenburg H., Kerrien S., Brinkman F.S.L., Ceol A., Chautard E., Dana J.M., De Las Rivas J., Dumousseau M., Galeota E., Gaulton A., Goll J., Hancock R.E.W., Isserlin R., Jimenez R.C., Kerssemakers J., Khadake J., Lynn D.J., Michaut M., O'Kelly G., Ono K., Orchard S., Prieto C., Razick S., Rigina O., Salwinski L., Simonovic M., Velankar S., Winter A., Wu G., Bader G.D., Cesareni G., Donaldson I.M., Eisenberg D., Kleywegt G.J., Overington J., Ricard-Blum S., Tyers M., Albrecht M., Hermjakob H.","PSICQUIC and PSISCORE: Accessing and scoring molecular interactions",2011,"Nature Methods",8,7,,528,529,,42,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79959846617&partnerID=40&md5=614d5a12a5a6468d500d1c575c943f48","European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Max Planck Institute for Informatics, Saarbrücken, Germany; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada; Institute for Research in Biomedicine, Barcelona, Spain; Department of Biology, University of Rome Tor Vergata, Rome, Italy; Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Université Lyon 1, Lyon, France; Ontario Institute for Cancer Research, Toronto, ON, Canada; Cancer Research Center, Instituto de Biología Molecular y Celular Del Cáncer, Universidad de Salamanca, Salamanca, Spain; Istituto di Ricovero e Cura A Carattere Scientifico, Fondazione S. Lucia, Rome, Italy; J. Craig Venter Institute, Rockville, MD, United States; Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Centre for Molecular and Biomolecular Informatics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; Animal and Bioscience Research Department, Animal and Grassland Research Innovation Centre, Teagasc, Ireland; University of California, Trey Ideker Lab, San Diego, School of Medicine, San Diego, CA, United States; Institute of Biotechnology of León, León, Spain; Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway; Biomedical Research Group, Department of Informatics, University of Oslo, Oslo, Norway; Center for Biological Sequence Analysis, BioCentrum, Technical University of Denmark, Kongens Lyngby, Denmark; University of California, Los Angeles, Department of Energy Institute for Genomics and Proteomics, Los Angeles, CA, United States; Faculty of Science, Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland; Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Department for Molecular Biosciences, University of Oslo, Oslo, Norway; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, United States; Howard Hughes Medical Institute, University of California, Los Angeles, CA, United States; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada","Aranda, B., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Blankenburg, H., Max Planck Institute for Informatics, Saarbrücken, Germany; Kerrien, S., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Brinkman, F.S.L., Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada; Ceol, A., Institute for Research in Biomedicine, Barcelona, Spain, Department of Biology, University of Rome Tor Vergata, Rome, Italy; Chautard, E., Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Université Lyon 1, Lyon, France, Ontario Institute for Cancer Research, Toronto, ON, Canada; Dana, J.M., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; De Las Rivas, J., Cancer Research Center, Instituto de Biología Molecular y Celular Del Cáncer, Universidad de Salamanca, Salamanca, Spain; Dumousseau, M., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Galeota, E., Department of Biology, University of Rome Tor Vergata, Rome, Italy, Istituto di Ricovero e Cura A Carattere Scientifico, Fondazione S. Lucia, Rome, Italy; Gaulton, A., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Goll, J., J. Craig Venter Institute, Rockville, MD, United States; Hancock, R.E.W., Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada; Isserlin, R., Donnelly Centre, University of Toronto, Toronto, ON, Canada; Jimenez, R.C., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Kerssemakers, J., Centre for Molecular and Biomolecular Informatics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; Khadake, J., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Lynn, D.J., Animal and Bioscience Research Department, Animal and Grassland Research Innovation Centre, Teagasc, Ireland; Michaut, M., Donnelly Centre, University of Toronto, Toronto, ON, Canada; O'Kelly, G., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Ono, K., University of California, Trey Ideker Lab, San Diego, School of Medicine, San Diego, CA, United States; Orchard, S., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Prieto, C., Cancer Research Center, Instituto de Biología Molecular y Celular Del Cáncer, Universidad de Salamanca, Salamanca, Spain, Institute of Biotechnology of León, León, Spain; Razick, S., Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway, Biomedical Research Group, Department of Informatics, University of Oslo, Oslo, Norway; Rigina, O., Center for Biological Sequence Analysis, BioCentrum, Technical University of Denmark, Kongens Lyngby, Denmark; Salwinski, L., University of California, Los Angeles, Department of Energy Institute for Genomics and Proteomics, Los Angeles, CA, United States; Simonovic, M., Faculty of Science, Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland; Velankar, S., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Winter, A., Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Wu, G., Ontario Institute for Cancer Research, Toronto, ON, Canada; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON, Canada; Cesareni, G., Department of Biology, University of Rome Tor Vergata, Rome, Italy, Istituto di Ricovero e Cura A Carattere Scientifico, Fondazione S. Lucia, Rome, Italy; Donaldson, I.M., Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway, Department for Molecular Biosciences, University of Oslo, Oslo, Norway; Eisenberg, D., University of California, Los Angeles, Department of Energy Institute for Genomics and Proteomics, Los Angeles, CA, United States, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, United States, Howard Hughes Medical Institute, University of California, Los Angeles, CA, United States; Kleywegt, G.J., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Overington, J., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; Ricard-Blum, S., Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Université Lyon 1, Lyon, France; Tyers, M., Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Albrecht, M., Max Planck Institute for Informatics, Saarbrücken, Germany; Hermjakob, H., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom",[No abstract available],,"documentation; letter; methodology; molecular interaction; priority journal; protein binding; protein interaction; quality control; register; Animals; Computational Biology; Databases, Factual; Humans; Protein Binding; Proteins; Software",,"Proteins",,,,"Hermjakob, H., (2004) Nat. Biotechnol., 22, pp. 177-183; Kerrien, S., (2007) BMC Biol., 5, p. 44; Shannon, P., (2003) Genome Res., 13, pp. 2498-2504; Blankenburg, H., (2009) Bioinformatics, 25, pp. 1321-1328; Orchard, S., (2007) Proteomics, 7, pp. 3436-3440","Aranda, B.; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, United Kingdom; email: baranda@ebi.ac.uk",,,,,,,,15487091,,,10.1038/nmeth.1637,21716279,"English","Nat. Methods",Letter,Scopus
"Tan C.S.H., Schoof E.M., Creixell P., Pasculescu A., Lim W.A., Pawson T., Bader G.D., Linding R.","Response to comment on ""positive selection of tyrosine loss in metazoan evolution""",2011,"Science",332,6032,,917,b,,2,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79956315380&partnerID=40&md5=3e0949e75c604308b5c45cdc983cbe15","Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada; Institute of Cancer Research (ICR), London, United Kingdom; Center for Biological Sequence Analysis (CBS), Department of Systems Biology, Technical University of Denmark (DTU), DK-2800 Lyngby, Denmark; Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, United States","Tan, C.S.H., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre, University of Toronto, Toronto, ON, Canada; Schoof, E.M., Institute of Cancer Research (ICR), London, United Kingdom, Center for Biological Sequence Analysis (CBS), Department of Systems Biology, Technical University of Denmark (DTU), DK-2800 Lyngby, Denmark; Creixell, P., Institute of Cancer Research (ICR), London, United Kingdom, Center for Biological Sequence Analysis (CBS), Department of Systems Biology, Technical University of Denmark (DTU), DK-2800 Lyngby, Denmark; Pasculescu, A., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Lim, W.A., Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, United States; Pawson, T., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bader, G.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre, University of Toronto, Toronto, ON, Canada; Linding, R., Institute of Cancer Research (ICR), London, United Kingdom, Center for Biological Sequence Analysis (CBS), Department of Systems Biology, Technical University of Denmark (DTU), DK-2800 Lyngby, Denmark","Su et al. claim guanine-cytosine (GC) content variation can largely explain the observed tyrosine frequency variation, independent of adaptive evolution of cell-signaling complexity. We found that GC content variation, in the absence of selection for amino acid changes, can only maximally account for 38% of the observed tyrosine frequency variation. We also uncovered other mechanisms acting to reduce tyrosine phosphorylation that further support our previous proposal.",,"phenylalanine; phosphotyrosine; protein tyrosine kinase; tryptophan; tyrosine; amino acid analysis; amino acid substitution; Anopheles gambiae; Caenorhabditis elegans; chicken; Ciona intestinalis; codon; controlled study; cow; DNA base composition; Drosophila melanogaster; gene frequency; gene loss; genetic variability; human; metazoon; molecular evolution; Monosiga brevicollis; mouse; natural selection; nonhuman; note; phenotype; phylogeny; priority journal; protein phosphorylation; puffer fish; rat; Saccharomyces cerevisiae; Schizosaccharomyces pombe; sequence analysis; signal transduction; Tetraodontiformes; Xenopus; zebra fish; Metazoa",,"phenylalanine, 3617-44-5, 63-91-2; phosphotyrosine, 21820-51-9; protein tyrosine kinase, 80449-02-1; tryptophan, 6912-86-3, 73-22-3; tyrosine, 16870-43-2, 55520-40-6, 60-18-4",,,,"Superti-Furga, G., Fumagalli, S., Koegl, M., Courtneidge, S.A., Draetta, G., (1993) EMBO J., 12, p. 2625; Superti-Furga, G., Jönsson, K., Courtneidge, S.A., (1996) Nat. Biotechnol., 14, p. 600; Tan, C.S.H., (2009) Science, 325, p. 1686; Linding, R., (2007) Cell, 129, p. 1415; Su, Z., Huang, W., Gu, X., (2011) Science, 332, p. 917. , www.sciencemag.org/cgi/content/full/332/6032/917-a; noteWood, S.N., (2006) Generalized Additive Models: An Introduction with R, , Chapman & Hall/CRC, Boca Raton, FL; Faraway, J.J., (2004) Linear Models with R, , Chapman & Hall/CRC, Boca Raton, FL; Henikoff, S., Henikoff, J.G., (1992) Proc. Natl. Acad. Sci. U.S.A., 89, p. 10915; Miller, M.L., (2008) Sci. Signal., 1, pp. ra2; Vinogradov, A.E., (2005) Trends Genet., 21, p. 639; Kudla, G., Lipinski, L., Caffin, F., Helwak, A., Zylicz, M., (2006) PLoS Biol., 4, pp. e180; Landolin, J.M., (2010) Genome Res., 20, p. 890; Manning, G., Young, S.L., Miller, W.T., Zhai, Y., (2008) Proc. Natl. Acad. Sci. U.S.A., 105, p. 9674; Tan, C.S.H., (2009) Sci. Signal., 2, pp. ra39; R Foundation for Statistical Computing, , www.R-project.org; Katoh, K., Toh, H., (2008) Brief. Bioinform., 9, p. 286","Linding, R.; Institute of Cancer Research (ICR), London, United Kingdom; email: linding@cbs.dtu.dk",,,,,,,,00368075,,SCIEA,10.1126/science.1188535,,"English","Science",Note,Scopus
"Gfeller D., Butty F., Wierzbicka M., Verschueren E., Vanhee P., Huang H., Ernst A., Dar N., Stagljar I., Serrano L., Sidhu S.S., Bader G.D., Kim P.M.","The multiple-specificity landscape of modular peptide recognition domains",2011,"Molecular Systems Biology",7,, 484,,,,21,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79955569676&partnerID=40&md5=524626033dc34f3d0604def118d3de02","Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada; EMBL-CRG Systems Biology Unit, CRG-Centre de Regulacio Genomica, Barcelona, Spain; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Computer Science, University of Toronto, Toronto, ON, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Swiss Institute of Bioinformatics, Molecular Modeling, Génopode, CH-1015 Lausanne, Switzerland","Gfeller, D., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada, Swiss Institute of Bioinformatics, Molecular Modeling, Génopode, CH-1015 Lausanne, Switzerland; Butty, F., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Wierzbicka, M., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Verschueren, E., EMBL-CRG Systems Biology Unit, CRG-Centre de Regulacio Genomica, Barcelona, Spain; Vanhee, P., EMBL-CRG Systems Biology Unit, CRG-Centre de Regulacio Genomica, Barcelona, Spain; Huang, H., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Ernst, A., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Dar, N., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Stagljar, I., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Serrano, L., EMBL-CRG Systems Biology Unit, CRG-Centre de Regulacio Genomica, Barcelona, Spain; Sidhu, S.S., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bader, G.D., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Computer Science, University of Toronto, Toronto, ON, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Kim, P.M., Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Biochemistry, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Computer Science, University of Toronto, Toronto, ON, Canada","Modular protein interaction domains form the building blocks of eukaryotic signaling pathways. Many of them, known as peptide recognition domains, mediate protein interactions by recognizing short, linear amino acid stretches on the surface of their cognate partners with high specificity. Residues in these stretches are usually assumed to contribute independently to binding, which has led to a simplified understanding of protein interactions. Conversely, we observe in large binding peptide data sets that different residue positions display highly significant correlations for many domains in three distinct families (PDZ, SH3 and WW). These correlation patterns reveal a widespread occurrence of multiple binding specificities and give novel structural insights into protein interactions. For example, we predict a new binding mode of PDZ domains and structurally rationalize it for DLG1 PDZ1. We show that multiple specificity more accurately predicts protein interactions and experimentally validate some of the predictions for the human proteins DLG1 and SCRIB. Overall, our results reveal a rich specificity landscape in peptide recognition domains, suggesting new ways of encoding specificity in protein interaction networks. © 2011 EMBO and Macmillan Publishers Limited All rights reserved.","binding specificity; PDZ; peptide recognition domains; phage display; residue correlations","Drosophila protein; PDZ protein; PDZ1 protein; peptide; protein DLG1; protein kinase; protein SH3; protein WW; unclassified drug; DLG1 protein, human; membrane protein; SCRIB protein, human; signal transducing adaptor protein; tumor suppressor protein; animal cell; article; cell specificity; controlled study; molecular recognition; nonhuman; prediction; priority journal; protein binding; protein domain; protein expression; protein function; protein protein interaction; protein structure; protein synthesis; signal transduction; yeast; amino acid sequence; animal; binding site; chemical structure; chemistry; cluster analysis; human; metabolism; molecular genetics; mouse; PDZ domain; protein analysis; protein binding; Src homology domain; systems biology; Eukaryota; Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Binding Sites; Cluster Analysis; Humans; Membrane Proteins; Mice; Models, Molecular; Molecular Sequence Data; PDZ Domains; Protein Binding; Protein Interaction Mapping; Signal Transduction; src Homology Domains; Systems Biology; Tumor Suppressor Proteins",,"protein kinase, 9026-43-1; Adaptor Proteins, Signal Transducing; DLG1 protein, human; Membrane Proteins; SCRIB protein, human; Tumor Suppressor Proteins",,,,"Aranda, B., Achuthan, P., Alam-Faruque, Y., Armean, I., Bridge, A., Derow, C., Feuermann, M., Van Eijk, K., The IntAct molecular interaction database in 2010 (2010) Nucleic Acids Res, 38, pp. D525-D531; Badis, G., Berger, M.F., Philippakis, A.A., Talukder, S., Gehrke, A.R., Jaeger, S.A., Chan, E.T., Bulyk, M.L., Diversity and complexity in DNA recognition by transcription factors (2009) Science, 324, pp. 1720-1723; Bailey, T.L., Elkan, C., Fitting a mixture model by expectation maximization to discover motifs in biopolymers (1994) Proc Int Conf Intell Syst Mol Biol, 2, pp. 28-36; 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D.; Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; email: gary.bader@utoronto.ca",,,,,,,,17444292,,,10.1038/msb.2011.18,21525870,"English","Mol. Syst. Biol.",Article,Scopus
"Oesper L., Merico D., Isserlin R., Bader G.D.","WordCloud: A Cytoscape plugin to create a visual semantic summary of networks",2011,"Source Code for Biology and Medicine",6,, 7,,,,3,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79953729967&partnerID=40&md5=c6ba00232fe9a23e3c3df1aa1c51d177","Department of Computer Science, Brown University, Providence, RI, United States; The Donnelly Centre, University of Toronto, Toronto, ON, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada","Oesper, L., Department of Computer Science, Brown University, Providence, RI, United States; Merico, D., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Isserlin, R., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Bader, G.D., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada","Background: When biological networks are studied, it is common to look for clusters, i.e. sets of nodes that are highly inter-connected. To understand the biological meaning of a cluster, the user usually has to sift through many textual annotations that are associated with biological entities.Findings: The WordCloud Cytoscape plugin generates a visual summary of these annotations by displaying them as a tag cloud, where more frequent words are displayed using a larger font size. Word co-occurrence in a phrase can be visualized by arranging words in clusters or as a network.Conclusions: WordCloud provides a concise visual summary of annotations which is helpful for network analysis and interpretation. WordCloud is freely available at http://baderlab.org/Software/WordCloudPlugin. © 2011 Oesper et al; licensee BioMed Central Ltd.",,,,,,,,"Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: a software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504. , 10.1101/gr.1239303, 403769, 14597658; Merico, D., Gfeller, D., Bader, G.D., How to visually interpret biological data using networks (2009) Nat Biotechnol, 27, pp. 921-924. , 10.1038/nbt.1567, 19816451; Krogan, N.J., Cagney, G., Yu, H., Zhong, G., Guo, X., Ignatchenko, A., Li, J., Greenblatt, J.F., Global landscape of protein complexes in the yeast Saccharomyces cerevisiae (2006) Nature, 440, pp. 637-643. , 10.1038/nature04670, 16554755; Gene Ontology: tool for the unification of biology (2000) Nat Genet, 25, pp. 25-29. , 10.1038/75556, 3037419, 10802651, Gene Ontology Consortium; Isserlin, R., Merico, D., Alikhani-Koupaei, R., Gramolini, A., Bader, G.D., Emili, A., Pathway Analysis of Dilated Cardiomyopathy using Global Proteomic Profiling and Enrichment Maps (2010) Proteomics, 10, pp. 1316-1327. , 10.1002/pmic.200900412, 2879143,2879143, 20127684; Hammond, T., Hannay, T., Lund, B., Scott, J., Social bookmarking tools (I): A general review (2005) D-Lib Magazine, 11 (4); Kuo, B.Y.L., Hentrich, T., Good, B.M., Wilkinson, M.D., Tag clouds for summarizing web search results (2007) Proceedings of the 16th International Conference on World Wide Web, , Banff, Alberta, Canada; Begelman, G., Keller, P., Smadja, F., Automated Tag Clustering: Improving search and exploration in the tag space (2006) Proceedings of the 15th International Conference on World Wide Web, , Edinburgh, UK; Hassan-Montero, Y., Herrero-Solana, V., Improving tag-clouds as visual information retrieval interfaces (2006) International Conference on Multidisciplinary Information Sciences and Technologies, , Merida, Spain; Nam, D., Kim, S.Y., Gene-set approach for expression pattern analysis (2008) Briefings in Bioinformatics, 9, pp. 189-197. , 10.1093/bib/bbn001, 18202032; Merico, D., Isserlin, R., Stueker, O., Emili, A., Bader, G.D., Enrichment Map A Network-Based Method for Gene-Set Enrichment Visualization and Interpretation (2010) PloS ONE, 5 (11). , 10.1371/journal.pone.0013984, 2981572, 21085593; Sartor, M.A., Mahavisno, V., Keshamouni, V.G., Cavalcoli, J., Wright, Z., Karnovsky, A., Kuick, R., Omenn, G.S., ConceptGen a gene set enrichment and gene set relation mapping tool (2010) Bioinformatics, 26, pp. 456-463. , 10.1093/bioinformatics/btp683, 2852214, 20007254; Bindea, G., Mlecnik, B., Hackl, H., Charoentong, P., Tosolini, M., Kirilovsky, A., Fridman, W.H., Galon, J., ClueGo: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks (2009) Bioinformatics, 25, pp. 1091-1093. , 10.1093/bioinformatics/btp101, 2666812, 19237447; Porter, M.F., An algorithm for suffix stripping (2006) Program: electronic library and information systems, 40, pp. 211-218","Oesper, L.; Department of Computer Science, Brown University, Providence, RI, United States; email: layla@cs.brown.edu",,,,,,,,17510473,,,10.1186/1751-0473-6-7,,"English","Source Code Biol. Med.",Article,Scopus
"Bellay J., Han S., Michaut M., Kim T., Costanzo M., Andrews B.J., Boone C., Bader G.D., Myers C.L., Kim P.M.","Bringing order to protein disorder through comparative genomics and genetic interactions",2011,"Genome Biology",12,2, R14,,,,21,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79851508882&partnerID=40&md5=dd510631dd19f2f2c2a739f8c130e2f3","Department of Computer Science and Engineering, University of Minnesota, 200 Union Street SE, Minneapolis, MN 55455, United States; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Computer Science, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","Bellay, J., Department of Computer Science and Engineering, University of Minnesota, 200 Union Street SE, Minneapolis, MN 55455, United States; Han, S., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Michaut, M., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Kim, T., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Costanzo, M., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Andrews, B.J., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Boone, C., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Bader, G.D., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Myers, C.L., Department of Computer Science and Engineering, University of Minnesota, 200 Union Street SE, Minneapolis, MN 55455, United States; Kim, P.M., The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","Background: Intrinsically disordered regions are widespread, especially in proteomes of higher eukaryotes. Recently, protein disorder has been associated with a wide variety of cellular processes and has been implicated in several human diseases. Despite its apparent functional importance, the sheer range of different roles played by protein disorder often makes its exact contribution difficult to interpret.Results: We attempt to better understand the different roles of disorder using a novel analysis that leverages both comparative genomics and genetic interactions. Strikingly, we find that disorder can be partitioned into three biologically distinct phenomena: regions where disorder is conserved but with quickly evolving amino acid sequences (flexible disorder); regions of conserved disorder with also highly conserved amino acid sequences (constrained disorder); and, lastly, non-conserved disorder. Flexible disorder bears many of the characteristics commonly attributed to disorder and is associated with signaling pathways and multi-functionality. Conversely, constrained disorder has markedly different functional attributes and is involved in RNA binding and protein chaperones. Finally, non-conserved disorder lacks clear functional hallmarks based on our analysis.Conclusions: Our new perspective on protein disorder clarifies a variety of previous results by putting them into a systematic framework. Moreover, the clear and distinct functional association of flexible and constrained disorder will allow for new approaches and more specific algorithms for disorder detection in a functional context. Finally, in flexible disordered regions, we demonstrate clear evolutionary selection of protein disorder with little selection on primary structure, which has important implications for sequence-based studies of protein structure and evolution. © 2011 Bellay et al.; licensee BioMed Central Ltd.",,"chaperone; heat shock protein 90; structural protein; protein; transcriptome; amino acid sequence; article; controlled study; gene function; gene interaction; genetic conservation; genomics; nonhuman; protein defect; protein RNA binding; protein structure; signal transduction; algorithm; chemistry; Escherichia coli; genetics; human; methodology; molecular evolution; molecular genetics; nucleotide sequence; protein database; protein folding; protein tertiary structure; statistical model; Eukaryota; Algorithms; Amino Acid Sequence; Conserved Sequence; Databases, Protein; Escherichia coli; Evolution, Molecular; Genomics; Humans; Models, Statistical; Molecular Sequence Data; Protein Folding; Protein Structure, Tertiary; Proteins; Transcriptome",,"protein, 67254-75-5; Proteins",,,,"Pauling, L., A theory of the structure and process of formation of antibodies. 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(2008) Science, 322, pp. 104-110. , 10.1126/science.1158684, 2746753, 18719252; Kim, P.M., Sboner, A., Xia, Y., Gerstein, M., The role of disorder in interaction networks: a structural analysis. (2008) Mol Syst Biol, 4, p. 179. , 10.1038/msb.2008.16, 2290937, 18364713","Myers, C.L.; Department of Computer Science and Engineering, University of Minnesota, 200 Union Street SE, Minneapolis, MN 55455, United States; email: cmyers@cs.umn.edu",,,,,,,,14747596,,GNBLF,10.1186/gb-2011-12-2-r14,21324131,"English","Genome Biol.",Article,Scopus
"Edwards A.M., Isserlin R., Bader G.D., Frye S.V., Willson T.M., Yu F.H.","Too many roads not taken",2011,"Nature",470,7333,,163,165,,47,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79951499644&partnerID=40&md5=b3d2e1332d70855c67650e6623a826ba","University of Toronto, Toronto, ON M5G 1L7, Canada; Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Center for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; GlaxoSmithKline, Research Triangle Park, NC 27709, United States; Program in Neurobiology, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea","Edwards, A.M., University of Toronto, Toronto, ON M5G 1L7, Canada; Isserlin, R., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Bader, G.D., Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Frye, S.V., Center for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Willson, T.M., GlaxoSmithKline, Research Triangle Park, NC 27709, United States; Yu, F.H., Program in Neurobiology, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea",[No abstract available],,"cell nucleus receptor; DNA; ion channel; protein; protein kinase; budget; cost; DNA microarray; human; human genome; medical research; note; priority journal; protein analysis; protein family; protein function; publication; research; science; United Kingdom; Bibliometrics; Biomedical Research; Human Genome Project; Humans; Ion Channels; Protein Kinases; Receptors, Cytoplasmic and Nuclear",,"DNA, 9007-49-2; protein, 67254-75-5; protein kinase, 9026-43-1; Ion Channels; Protein Kinases, 2.7.-; Receptors, Cytoplasmic and Nuclear",,,,"Isserlin, R., (2011), http://arxiv.org/abs/1102.0448, Preprint atGrueneberg, D.A., (2008) Proc. Natl Acad. Sci. USA, 105, pp. 16472-16477; Fedorov, O., Müller, S., Knapp, S., (2010) Nature Chem. Biol, 6, pp. 166-169; Frye, S.V., (2010) Nature Chem. Biol, 6, pp. 159-161; Willson, T.M., Moore, J.T., (2002) Mol. Endocrinol, 16, pp. 1135-1144; Muscatelli, F., (1994) Nature, 372, pp. 672-676; Yamagata, K., (1996) Nature, 384, pp. 458-460; Achermann, J.C., Ito, M., Ito, M., Hindmarsh, P.C., Jameson, J.L., (1999) Nature Genet, 22, pp. 125-126; Lee, S.L., (1996) Science, 273, pp. 1219-1221","Edwards, A. M.; University of Toronto, Toronto, ON M5G 1L7, Canada; email: aled.edwards@utoronto.ca",,,,,,,,00280836,,NATUA,10.1038/470163a,21307913,"English","Nature",Note,Scopus
"Michaut M., Baryshnikova A., Costanzo M., Myers C.L., Andrews B.J., Boone C., Bader G.D.","Protein complexes are central in the yeast genetic landscape",2011,"PLoS Computational Biology",7,2, e1001092,,,,17,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79952474742&partnerID=40&md5=98ab53cc18a2e31f645026d7390734ba","The Donnelly Centre, University of Toronto, Toronto, ON, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Computer Science, University of Toronto, Toronto, ON, Canada; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, United States","Michaut, M., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Baryshnikova, A., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Costanzo, M., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Myers, C.L., Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, United States; Andrews, B.J., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Boone, C., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bader, G.D., The Donnelly Centre, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Department of Computer Science, University of Toronto, Toronto, ON, Canada","If perturbing two genes together has a stronger or weaker effect than expected, they are said to genetically interact. Genetic interactions are important because they help map gene function, and functionally related genes have similar genetic interaction patterns. Mapping quantitative (positive and negative) genetic interactions on a global scale has recently become possible. This data clearly shows groups of genes connected by predominantly positive or negative interactions, termed monochromatic groups. These groups often correspond to functional modules, like biological processes or complexes, or connections between modules. However it is not yet known how these patterns globally relate to known functional modules. Here we systematically study the monochromatic nature of known biological processes using the largest quantitative genetic interaction data set available, which includes fitness measurements for ~5.4 million gene pairs in the yeast Saccharomyces cerevisiae. We find that only 10% of biological processes, as defined by Gene Ontology annotations, and less than 1% of inter-process connections are monochromatic. Further, we show that protein complexes are responsible for a surprisingly large fraction of these patterns. This suggests that complexes play a central role in shaping the monochromatic landscape of biological processes. Altogether this work shows that both positive and negative monochromatic patterns are found in known biological processes and in their connections and that protein complexes play an important role in these patterns. The monochromatic processes, complexes and connections we find chart a hierarchical and modular map of sensitive and redundant biological systems in the yeast cell that will be useful for gene function prediction and comparison across phenotypes and organisms. Furthermore the analysis methods we develop are applicable to other species for which genetic interactions will progressively become more available. © 2011 Michaut et al.",,"fungal protein; article; complex formation; controlled study; fungal genetics; gene function; gene interaction; gene mapping; nonhuman; phenotype; prediction; protein analysis; protein function; Saccharomyces cerevisiae; yeast cell; Saccharomyces cerevisiae",,,,,,"Giaever, G., Chu, A.M., Ni, L., Connelly, C., Riles, L., Functional profiling of the Saccharomyces cerevisiae genome (2002) Nature, 418, pp. 387-391; Hillenmeyer, M.E., Fung, E., Wildenhain, J., Pierce, S.E., Hoon, S., The chemical genomic portrait of yeast: uncovering a phenotype for all genes (2008) Science, 320, pp. 362-365; Tong, A.H., Evangelista, M., Parsons, A.B., Xu, H., Bader, G.D., Systematic genetic analysis with ordered arrays of yeast deletion mutants (2001) Science, 294, pp. 2364-2368; Schuldiner, M., Collins, S.R., Thompson, N.J., Denic, V., Bhamidipati, A., Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile (2005) Cell, 123, pp. 507-519; Pan, X., Yuan, D.S., Ooi, S.-L., Wang, X., Sookhai-Mahadeo, S., dSLAM analysis of genome-wide genetic interactions in Saccharomyces cerevisiae (2007) Methods, 41, pp. 206-221; Tong, A.H.Y., Lesage, G., Bader, G.D., Ding, H., Xu, H., Global mapping of the yeast genetic interaction network (2004) Science, 303, pp. 808-813; Costanzo, M., Baryshnikova, A., Bellay, J., Kim, Y., Spear, E.D., The genetic landscape of a cell (2010) Science, 327, pp. 425-431; Breslow, D.K., Cameron, D.M., Collins, S.R., Schuldiner, M., Stewart-Ornstein, J., A comprehensive strategy enabling high-resolution functional analysis of the yeast genome (2008) Nat Methods, 5, pp. 711-718; Fiedler, D., Braberg, H., Mehta, M., Chechik, G., Cagney, G., Functional organization of the S. cerevisiae phosphorylation network (2009) Cell, 136, pp. 952-963; Wong, S.L., Zhang, L.V., Roth, F.P., Discovering functional relationships: biochemistry versus genetics (2005) Trends Genet, 21, pp. 424-427; Mani, R., St Onge, R.P., Hartman, J.L., Giaever, G., Roth, F.P., Defining genetic interaction (2008) Proc Natl Acad Sci USA, 105, pp. 3461-3466; Tucker, C.L., Fields, S., Lethal combinations (2003) Nat Genet, 35, pp. 204-205; Boone, C., Bussey, H., Andrews, B.J., Exploring genetic interactions and networks with yeast (2007) Nat Rev Genet, 8, pp. 437-449; Le Meur, N., Gentleman, R., Modeling synthetic lethality (2008) Genome Biol, 9, pp. R135; Brady, A., Maxwell, K., Daniels, N., Cowen, L.J., Fault tolerance in protein interaction networks: stable bipartite subgraphs and redundant pathways (2009) PLoS One, 4, pp. e5364; Hartman, J.L.T., Garvik, B., Hartwell, L., Principles for the buffering of genetic variation (2001) Science, 291, pp. 1001-1004; Kelley, R., Ideker, T., Systematic interpretation of genetic interactions using protein networks (2005) Nat Biotechnol, 23, pp. 561-566; Ulitsky, I., Shamir, R., Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks (2007) Mol Syst Biol, 3, p. 104; Ulitsky, I., Shlomi, T., Kupiec, M., Shamir, R., From E-MAPs to module maps: dissecting quantitative genetic interactions using physical interactions (2008) Mol Syst Biol, 4, p. 209; Bandyopadhyay, S., Kelley, R., Krogan, N.J., Ideker, T., Functional maps of protein complexes from quantitative genetic interaction data (2008) PLoS Comput Biol, 4, pp. e1000065; Breker, M., Schuldiner, M., Explorations in topology-delving underneath the surface of genetic interaction maps (2009) Mol Biosyst, 5, pp. 1473-1481; Segre, D., Deluna, A., Church, G.M., Kishony, R., Modular epistasis in yeast metabolism (2005) Nat Genet, 37, pp. 77-83; Ye, P., Peyser, B.D., Pan, X., Boeke, J.D., Spencer, F.A., Gene function prediction from congruent synthetic lethal interactions in yeast (2005) Mol Syst Biol, 1, p. 20050026; Collins, S.R., Schuldiner, M., Krogan, N.J., Weissman, J.S., A strategy for extracting and analyzing large-scale quantitative epistatic interaction data (2006) Genome Biol, 7, pp. R63; Baryshnikova, A., Costanzo, M., Kim, Y., Ding, H., Koh, J., Quantitative analysis of fitness and genetic interactions in yeast on a genome scale (2010) Nat Methods, 7, pp. 1017-1024; Pu, S., Ronen, K., Vlasblom, J., Greenblatt, J., Wodak, S.J., Local coherence in genetic interaction patterns reveals prevalent functional versatility (2008) Bioinformatics, 24, pp. 2376-2383; Jaimovich, A., Rinott, R., Schuldiner, M., Margalit, H., Friedman, N., Modularity and directionality in genetic interaction maps (2010) Bioinformatics, 26, pp. i228-i236; Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Gene ontology: tool for the unification of biology. The Gene Ontology Consortium (2000) Nat Genet, 25, pp. 25-29; Benschop, J.J., Brabers, N., van Leenen, D., Bakker, L.V., van Deutekom, H.W., A consensus of core protein complex compositions for Saccharomyces cerevisiae (2010) Mol Cell, 38, pp. 916-928; Pu, S., Wong, J., Turner, B., Cho, E., Wodak, S.J., Up-to-date catalogues of yeast protein complexes (2009) Nucleic Acids Res, 37, pp. 825-831; Hart, G.T., Lee, I., Marcotte, E.R., A high-accuracy consensus map of yeast protein complexes reveals modular nature of gene essentiality (2007) BMC Bioinformatics, 8, p. 236; Musso, G., Costanzo, M., Huangfu, M., Smith, A.M., Paw, J., The extensive and condition-dependent nature of epistasis among whole-genome duplicates in yeast (2008) Genome Res, 18, pp. 1092-1099; Ruepp, A., Zollner, A., Maier, D., Albermann, K., Hani, J., The FunCat, a functional annotation scheme for systematic classification of proteins from whole genomes (2004) Nucleic Acids Res, 32, pp. 5539-5545; Vizeacoumar, F.J., Chong, Y., Boone, C., Andrews, B.J., A picture is worth a thousand words: genomics to phenomics in the yeast Saccharomyces cerevisiae (2009) FEBS Lett, 583, pp. 1656-1661; Vizeacoumar, F.J., van Dyk, N.F.S.V., Cheung, V., Li, J., Integrating high-throughput genetic interaction mapping and high-content screening to explore yeast spindle morphogenesis (2010) J Cell Biol, 188, pp. 69-81; Byrne, A.B., Weirauch, M.T., Wong, V., Koeva, M., Dixon, S.J., A global analysis of genetic interactions in Caenorhabditis elegans (2007) J Biol, 6, p. 8; Lehner, B., Crombie, C., Tischler, J., Fortunato, A., Fraser, A.G., Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways (2006) Nat Genet, 38, pp. 896-903; Tweedie, S., Ashburner, M., Falls, K., Leyland, P., McQuilton, P., FlyBase: enhancing Drosophila Gene Ontology annotations (2009) Nucleic Acids Res, 37, pp. D555-D559; Hong, E.L., Balakrishnan, R., Dong, Q., Christie, K.R., Park, J., Gene Ontology annotations at SGD: new data sources and annotation methods (2008) Nucleic Acids Res, 36, pp. D577-D581; Myers, C.L., Barrett, D.R., Hibbs, M.A., Huttenhower, C., Troyanskaya, O.G., Finding function: evaluation methods for functional genomic data (2006) BMC Genomics, 7, p. 187; Baudin, A., Ozier-Kalogeropoulos, O., Denouel, A., Lacroute, F., Cullin, C., A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae (1993) Nucleic Acids Res, 21, pp. 3329-3330; Byrne, K.P., Wolfe, K.H., The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species (2005) Genome Res, 15, pp. 1456-1461; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Cytoscape: a software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504","Bader, G. D.; The Donnelly Centre, University of Toronto, Toronto, ON, Canada; email: gary.bader@utoronto.ca",,,,,,,,1553734X,,,10.1371/journal.pcbi.1001092,,"English","PLoS Comput. Biol.",Article,Scopus
"Shao X., Tan C.S.H., Voss C., Li S.S.C., Deng N., Bader G.D.","A regression framework incorporating quantitative and negative interaction data improves quantitative prediction of PDZ domain-peptide interaction from primary sequence",2011,"Bioinformatics",27,3, btq657,383,390,,11,"http://www.scopus.com/inward/record.url?eid=2-s2.0-79551614773&partnerID=40&md5=1bae65cafc3fbf423ec03ca9df7d20c4","Department of Applied Mathematics, College of Science, China Agricultural University, Beijing, 100083, China; Banting and Best Department of Medical Research, University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Western Ontario, London, ON N6A 5B8, Canada","Shao, X., Department of Applied Mathematics, College of Science, China Agricultural University, Beijing, 100083, China, Banting and Best Department of Medical Research, University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada; Tan, C.S.H., Banting and Best Department of Medical Research, University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada; Voss, C., Department of Biochemistry, University of Western Ontario, London, ON N6A 5B8, Canada; Li, S.S.C., Department of Biochemistry, University of Western Ontario, London, ON N6A 5B8, Canada; Deng, N., Department of Applied Mathematics, College of Science, China Agricultural University, Beijing, 100083, China; Bader, G.D., Banting and Best Department of Medical Research, University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada","Motivation: Predicting protein interactions involving peptide recognition domains is essential for understanding the many important biological processes they mediate. It is important to consider the binding strength of these interactions to help us construct more biologically relevant protein interaction networks that consider cellular context and competition between potential binders. Results: We developed a novel regression framework that considers both positive (quantitative) and negative (qualitative) interaction data available for mouse PDZ domains to quantitatively predict interactions between PDZ domains, a large peptide recognition domain family, and their peptide ligands using primary sequence information. First, we show that it is possible to learn from existing quantitative and negative interaction data to infer the relative binding strength of interactions involving previously unseen PDZ domains and/or peptides given their primary sequence. Performance was measured using cross-validated hold out testing and testing with previously unseen PDZ domain-peptide interactions. Second, we find that incorporating negative data improves quantitative interaction prediction. Third, we show that sequence similarity is an important prediction performance determinant, which suggests that experimentally collecting additional quantitative interaction data for underrepresented PDZ domain subfamilies will improve prediction. © The Author(s) 2010. Published by Oxford University Press.",,"ligand; peptide; protein; animal; article; biology; chemical structure; chemistry; genetics; metabolism; methodology; mouse; mutation; PDZ domain; protein binding; protein tertiary structure; regression analysis; reproducibility; Animals; Computational Biology; Ligands; Mice; Models, Molecular; Mutation; PDZ Domains; Peptides; Protein Binding; Protein Structure, Tertiary; Proteins; Regression Analysis; Reproducibility of Results",,"protein, 67254-75-5; Ligands; Peptides; Proteins",,,,"Atchley, W.R., Solving the protein sequence metric problem (2005) Proc Natl Assoc Sci. USA, 102, pp. 6395-6400; Beuming, T., High-energy water sites determine peptide binding affinity and specificity of PDZ domains (2009) Protein Sci., 18, pp. 1609-1619; Castagnoli, L., Selectivity and promiscuity in the interaction network mediated by protein recognition modules (2004) FEBS Lett., 567, pp. 74-79; Chang, C.-C., Lin, C.-J., (2001) LIBSVM: a library for support vector machines, , http://www.csie.ntu.edu.tw/~cjlin/libsvm, Software available at; Chechik, G., Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network (2008) Nat. Biotechonol., 26, pp. 1251-1259; Chen, J.R., Predicting PDZ domain-peptide interactions from primary sequences (2008) Nat. Biotechonol., 26, pp. 1041-1045; Cushing, P.R., The relative binding affinities of PDZ partners for CFTR: a biochemical basis for efficient endocytic recycling (2008) Biochemistry, 47, pp. 10084-10098; Ernst, A., Rapid evolution of functional complexity in a domain family (2009) Sci. Signal., 2, pp. ra50; Ferraro, E., A novel structure-based encoding for machine-learning applied to the inference of SH3 domain specificity (2006) Bioinformatics, 22, pp. 2333-2339; Gibson, T.J., Cell regulation: determined to signal discrete cooperation (2009) Trends Biochem. Sci., 34, pp. 471-482; Halabi, N., Protein sectors: evolutionary units of three-dimensional structure (2009) Cell, 138, pp. 774-786; Hu, H., Amap of WWdomain family interactions (2004) Proteomics, 4, pp. 643-655; Huang, H., Defining the specificity space of the human Src homology 2 domain (2008) Mol. Cell. Proteomics, 7, pp. 768-784; Hue, M., Large-scale prediction of protein-protein interactions from structures (2010) BMC Bioinformatics, 11, p. 144; Jacob, L., Vert, J.-P., Efficient peptide-MHC-I binding prediction for alleles with few known binders (2008) Bioinformatics, 24, pp. 358-366; Jones, R.B., Aquantitative protein interaction network for the ErbB receptors using protein microarrays (2006) Nature, 439, pp. 168-174; Landgraf, C., Protein interaction networks by proteome peptide scanning (2004) PLoS Biol., 2, pp. E14; Lew, E.D., The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations (2009) Sci. Signal., 2, pp. ra6; Li, Z.R., PROFEAT: a web server for computing structural and physicochemical features of proteins and peptides from amino acid sequence (2006) Nucleic Acids Res., 34, pp. W32-W37; Liu, W., Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models (2006) BMC Bioinformatics, 7, p. 182; Lockless, S.W., Ranganathan, R., Evolutionarily conserved pathways of energetic connectivity in protein families (1999) Science, 286, pp. 295-299; Mangasarian, O.L., Knowledge-based kernel approximation (2004) J. Mach. Learn. Res., 5, pp. 1127-1141; Mangasarian, O.L., Wild, E.W., Nonlinear knowledge in kernel approximation (2007) IEEE Trans. Neural Netw., 18, pp. 300-306; Nielsen, M., Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan (2008) PLoS Comput. Biol., 4, pp. e1000107; Nourry, C., PDZ domain proteins: plug and play! (2003) Sci. 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Soc., 128, pp. 5913-5922; Stiffler, M.A., PDZ domain binding selectivity is optimized across the mouse proteome (2007) Science, 317, pp. 364-369; Stormo, G.D., DNA binding sites: representation and discovery (2000) Bioinformatics, 16, pp. 16-23; A second generation human haplotype map of over 3.1 million SNPs (2007) Nature, 449, pp. 851-861. , The International HapMap Consortium; Tong, A.H., A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules (2002) Science, 295, pp. 321-324; Tonikian, R., A specificity map for the PDZ domain family (2008) PLoS Biol., 6, pp. e239; Tonikian, R., Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins (2009) PLoS Biol., 7, pp. e1000218; Vogel, C., Structure, function and evolution of multidomain proteins (2004) Curr. Opin. Struct. Biol., 14, pp. 208-216; Wunderlich, Z., Mirny, L.A., Using genome-wide measurements for computational prediction of SH2-peptide interactions (2009) Nucleic Acids Res., 37, pp. 4629-4641; Yaffe, M.B., A motif-based profile scanning approach for genome-wide prediction of signaling pathways (2001) Nat. Biotechnol., 19, pp. 348-353; Zarrinpar, A., Optimization of specificity in a cellular protein interaction network by negative selection (2003) Nature, 426, pp. 676-680; Zhang, H., Pan-specific MHC class I predictors: a benchmark of HLA class I pan-specific prediction methods (2009) Bioinformatics, 25, pp. 83-89","Bader, G.D.; Banting and Best Department of Medical Research, University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON M5S 3E1, Canada; email: gary.bader@utoronto.ca",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/btq657,21127034,"English","Bioinformatics",Article,Scopus
"Cerami E.G., Gross B.E., Demir E., Rodchenkov I., Babur O., Anwar N., Schultz N., Bader G.D., Sander C.","Pathway Commons, a web resource for biological pathway data",2011,"Nucleic Acids Research",39,SUPPL. 1,,D685,D690,,83,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78651332286&partnerID=40&md5=a958a96921a0a7105d326bdc76ac6607","Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; Tri-Institutional Training Program in Computational Biology and Medicine, New York, United States; Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada","Cerami, E.G., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States, Tri-Institutional Training Program in Computational Biology and Medicine, New York, United States; Gross, B.E., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; Demir, E., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; Rodchenkov, I., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Babur, O., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; Anwar, N., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; Schultz, N., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; Bader, G.D., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States","Pathway Commons (http://www.pathwaycommons .org) is a collection of publicly available pathway data from multiple organisms. Pathway Commons provides a web-based interface that enables biologists to browse and search a comprehensive collection of pathways from multiple sources represented in a common language, a download site that provides integrated bulk sets of pathway information in standard or convenient formats and a web service that software developers can use to conveniently query and access all data. Database providers can share their pathway data via a common repository. Pathways include biochemical reactions, complex assembly, transport and catalysis events and physical interactions involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims to collect and integrate all public pathway data available in standard formats. Pathway Commons currently contains data from nine databases with over 1400 pathways and 687 000 interactions and will be continually expanded and updated. © The Author(s) 2010.",,"DNA; protein derivative; RNA; access to information; article; biochemistry; bioinformatics; catalysis; computer interface; computer language; computer program; data base; information processing; Internet; molecular interaction; priority journal; Databases, Factual; Databases, Genetic; Databases, Protein; Disease; Genomics; Internet; Models, Biological; Systems Integration; User-Computer Interface",,"DNA, 9007-49-2; RNA, 63231-63-0",,,,"Huang Da, W., Sherman, B.T., Lempicki, R.A., Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists (2009) Nucleic Acids Res., 37, pp. 1-13; Cerami, E., Demir, E., Schultz, N., Taylor, B.S., Sander, C., Automated network analysis identifies core pathways in glioblastoma (2010) PLoS One, 5, pp. e8918; Chuang, H.Y., Lee, E., Liu, Y.T., Lee, D., Ideker, T., Network-based classification of breast cancer metastasis (2007) Mol. 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G.; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10065, United States; email: pc-info@pathwaycommons.org",,,,,,,,03051048,,NARHA,10.1093/nar/gkq1039,21071392,"English","Nucleic Acids Res.",Article,Scopus
"Oka T., Remue E., Meerschaert K., Vanloo B., Boucherie C., Gfeller D., Bader G.D., Sidhu S.S., Vandekerckhove J., Gettemans J., Sudol M.","Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling",2010,"Biochemical Journal",432,3,,461,472,,19,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78649892579&partnerID=40&md5=8d94c59599b888fd5244809dd58c2cd9","Weis Center for Research, 100 North Academy Avenue, Danville, PA 17822, United States; Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium; Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, United States","Oka, T., Weis Center for Research, 100 North Academy Avenue, Danville, PA 17822, United States; Remue, E., Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Meerschaert, K., Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Vanloo, B., Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Boucherie, C., Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Gfeller, D., Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Bader, G.D., Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Sidhu, S.S., Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Vandekerckhove, J., Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Gettemans, J., Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium, Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Albert Baertsoenkaai 3, B-9000 Ghent, Belgium; Sudol, M., Weis Center for Research, 100 North Academy Avenue, Danville, PA 17822, United States, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, United States","The Hippo pathway regulates the size of organs by controlling two opposing processes: proliferation and apoptosis. YAP2 (Yes kinase-associated protein 2), one of the three isoforms of YAP, is a WW domain-containing transcriptional co-activator that acts as the effector of the Hippo pathway in mammalian cells. In addition to WW domains, YAP2 has a PDZ-binding motif at its C-terminus. We reported previously that this motif was necessary for YAP2 localization in the nucleus and for promoting cell detachment and apoptosis. In the present study, we show that the tight junction protein ZO (zonula occludens)-2 uses its first PDZ domain to form a complex with YAP2. The endogenous ZO-2 and YAP2 proteins co-localize in the nucleus. We also found that ZO-2 facilitates the nuclear localization and pro-apoptotic function of YAP2, and that this activity of ZO-2 is PDZ-domain-dependent. The present paper is the first report on a PDZ-based nuclear translocation mechanism. Moreover, since the Hippo pathway acts as a tumour suppressor pathway, the YAP2-ZO-2 complex could represent a target for cancer therapy. © The Authors Journal compilation © 2010 Biochemical Society.","Hippo pathway; Nuclear translocation; PDZ domain; Yes kinase-associated protein 2 (YAP2); Zona occludens protein","Hippo pathway; Nuclear translocations; PDZ domains; Yes kinase-associated protein 2 (YAP2); Zona occludens; Cell death; Mammals; Proteins; protein kinase Yes; protein ZO2; animal cell; animal experiment; article; cancer therapy; cell nucleus; mouse; nonhuman; nuclear localization signal; PDZ domain; priority journal; protein localization; tumor suppressor gene; Adaptor Proteins, Signal Transducing; Animals; Cell Adhesion; Cell Line; Cell Nucleus; Cell Proliferation; Dogs; Genes, Reporter; HEK293 Cells; Humans; Immunoprecipitation; Membrane Proteins; Mutant Proteins; PDZ Domains; Phosphoproteins; Protein Transport; Recombinant Fusion Proteins; RNA Interference; Signal Transduction; Transfection; Mammalia",,"Adaptor Proteins, Signal Transducing; Membrane Proteins; Mutant Proteins; Phosphoproteins; Recombinant Fusion Proteins; YAP1 protein, human; zonula occludens-1 protein; zonula occludens-2 protein",,,,"Harvey, K., Tapon, N., The Salvador-Warts-Hippo pathway: An emerging tumour-suppressor network (2007) Nat. 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"Merico D., Isserlin R., Stueker O., Emili A., Bader G.D.","Enrichment map: A network-based method for gene-set enrichment visualization and interpretation",2010,"PLoS ONE",5,11, e13984,,,,65,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78649775562&partnerID=40&md5=2ed1ac05a31c6758b087c88214a1993a","Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada","Merico, D., Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada; Isserlin, R., Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada; Stueker, O., Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada; Emili, A., Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada; Bader, G.D., Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada","Background: Gene-set enrichment analysis is a useful technique to help functionally characterize large gene lists, such as the results of gene expression experiments. This technique finds functionally coherent gene-sets, such as pathways, that are statistically over-represented in a given gene list. Ideally, the number of resulting sets is smaller than the number of genes in the list, thus simplifying interpretation. However, the increasing number and redundancy of gene-sets used by many current enrichment analysis software works against this ideal. Principal Findings: To overcome gene-set redundancy and help in the interpretation of large gene lists, we developed ""Enrichment Map"", a network-based visualization method for gene-set enrichment results. Gene-sets are organized in a network, where each set is a node and edges represent gene overlap between sets. Automated network layout groups related gene-sets into network clusters, enabling the user to quickly identify the major enriched functional themes and more easily interpret the enrichment results. Conclusions: Enrichment Map is a significant advance in the interpretation of enrichment analysis. Any research project that generates a list of genes can take advantage of this visualization framework. Enrichment Map is implemented as a freely available and user friendly plug-in for the Cytoscape network visualization software. © 2010 Merico et al.",,"anaphase promoting complex; estrogen; article; automation; breast cancer; cancer cell; cell cycle; chromatin immunoprecipitation; controlled study; DNA hybridization; down regulation; enrichment culture; gene cluster; gene mapping; genetic database; human; human cell; methodology; microtubule; protein degradation; upregulation; algorithm; biology; breast tumor; cluster analysis; colon tumor; computer program; drug effect; female; gene expression profiling; gene expression regulation; gene regulatory network; genetics; Internet; reproducibility; Algorithms; Breast Neoplasms; Cluster Analysis; Colonic Neoplasms; Computational Biology; Estrogens; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Internet; Reproducibility of Results; Software",,"anaphase promoting complex, 74812-49-0; Estrogens",,,,"Allison, D.B., Cui, X., Page, G.P., Sabripour, M., Microarray data analysis: From disarray to consolidation and consensus (2006) Nature Reviews Genetics, 7, pp. 55-65; Calarco, J.A., Saltzman, A.L., Ip, J.Y., Blencowe, B.J., Technologies for the global discovery and analysis of alternative splicing (2007) Advances In Experimental Medicine and Biology, 623, pp. 64-84; Nesvizhskii, A.I., Vitek, O., Aebersold, R., Analysis and validation of proteomic data generated by tandem mass spectrometry (2007) Nature Methods, 4, pp. 787-797; Quackenbush, J., Computational analysis of microarray data (2001) Nature Reviews Genetics, 2, pp. 418-427; Nam, D., Kim, S.-Y., Gene-set approach for expression pattern analysis (2008) Briefings In Bioinformatics, 9, pp. 189-197; Khatri, P., Draghici, S., Ostermeier, G.C., Krawetz, S.A., Profiling gene expression using onto-express (2002) Genomics, 79, pp. 266-270; Robinson, M.D., Grigull, J., Mohammad, N., Hughes, T.R., FunSpec: A webbased cluster interpreter for yeast (2002) BMC Bioinformatics, 3, p. 35; Draghici, S., Khatri, P., Martins, R.P., Ostermeier, G.C., Krawetz, S.A., Global functional profiling of gene expression (2003) Genomics, 81, pp. 98-104; Huang, D.W., Sherman, B.T., Lempicki, R.A., Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists (2009) Nucleic Acids Research, 37, pp. 1-13; Khatri, P., Drǎghici, S., Ontological analysis of gene expression data: Current tools, limitations, and open problems (2005) Bioinformatics (Oxford England), 21, pp. 3587-3595; Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Gene ontology: Tool for the unification of biology. 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D.; Department of Molecular Genetics Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Ontario, Canada; email: gary.bader@utoronto.ca",,,,,,,,19326203,,,10.1371/journal.pone.0013984,21085593,"English","PLoS ONE",Article,Scopus
"Baryshnikova A., Costanzo M., Kim Y., Ding H., Koh J., Toufighi K., Youn J.-Y., Ou J., San Luis B.-J., Bandyopadhyay S., Hibbs M., Hess D., Gingras A.-C., Bader G.D., Troyanskaya O.G., Brown G.W., Andrews B., Boone C., Myers C.L.","Quantitative analysis of fitness and genetic interactions in yeast on a genome scale",2010,"Nature Methods",7,12,,1017,1024,,50,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78649705725&partnerID=40&md5=3eb946d2d45b16713e43951bfb280f6c","Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, United States; Department of Electrical and Computer Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, United States; Department of Biochemistry, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Jackson Laboratory, Bar Harbor, ME, United States; Department of Biology, Santa Clara University, Santa Clara, CA, United States; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, United States","Baryshnikova, A., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Costanzo, M., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Kim, Y., Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, United States, Department of Electrical and Computer Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, United States; Ding, H., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Koh, J., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Toufighi, K., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Youn, J.-Y., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Ou, J., Department of Biochemistry, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; San Luis, B.-J., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Bandyopadhyay, S., Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, United States; Hibbs, M., Jackson Laboratory, Bar Harbor, ME, United States; Hess, D., Department of Biology, Santa Clara University, Santa Clara, CA, United States; Gingras, A.-C., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; Bader, G.D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Troyanskaya, O.G., Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, United States; Brown, G.W., Department of Biochemistry, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Andrews, B., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Boone, C., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; Myers, C.L., Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, United States","Global quantitative analysis of genetic interactions is a powerful approach for deciphering the roles of genes and mapping functional relationships among pathways. Using colony size as a proxy for fitness, we developed a method for measuring fitness-based genetic interactions from high-density arrays of yeast double mutants generated by synthetic genetic array (SGA) analysis. We identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate single- and double-mutant fitness measurements, which rival the accuracy of other high-resolution studies. We applied the SGA score to examine the relationship between physical and genetic interaction networks, and we found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles. © 2010 Nature America, Inc. All rights reserved.",,"article; fitness; fungal genetics; gene interaction; genome; nonhuman; priority journal; quantitative analysis; yeast; Algorithms; Gene Expression Regulation, Fungal; Genetic Fitness; Genome, Fungal; Genome-Wide Association Study; Mutagenesis; Mutation; Oligonucleotide Array Sequence Analysis; Ultraviolet Rays; Yeasts",,,,,,"Baryshnikova, A., Synthetic genetic array (SGA) analysis in Saccharomyces cerevisiae and Schizosaccharomyces pombe (2010) Methods Enzymol., 470, pp. 146-180; Dixon, S.J., Costanzo, M., Baryshnikova, A., Andrews, B., Boone, C., Systematic mapping of genetic interaction networks (2009) Annu. Rev. 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USA, 105, pp. 7111-7112; Hayashi, M., Fukuzawa, T., Sorimachi, H., Maeda, T., Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway (2005) Mol. Cell. Biol., 25, pp. 9478-9490; Barwell, K.J., Boysen, J.H., Xu, W., Mitchell, A.P., Relationship of DFG16 to the Rim101p pH response pathway in Saccharomyces cerevisiae and Candida albicans (2005) Eukaryot. Cell, 4, pp. 890-899; Rothfels, K., Components of the ESCRT pathway, DFG16, and YGR122w are required for Rim101 to act as a corepressor with Nrg1 at the negative regulatory element of the DIT1 gene of Saccharomyces cerevisiae (2005) Mol. Cell. Biol., 25, pp. 6772-6788; Kemp, H.A., Sprague Jr., G.F., Far3 and fve interacting proteins prevent premature recovery from pheromone arrest in the budding yeast Saccharomyces cerevisiae (2003) Mol. Cell. Biol., 23, pp. 1750-1763; Goudreault, M., A PP2A phosphatase high density interaction network identifes a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein (2009) Mol. Cell. Proteomics, 8, pp. 157-171; Posas, F., The gene PPG encodes a novel yeast protein phosphatase involved in glycogen accumulation (1993) J. Biol. Chem., 268, pp. 1349-1354; Van Driessche, N., Epistasis analysis with global transcriptional phenotypes (2005) Nat. Genet., 37, pp. 471-477; Dixon, S.J., Signifcant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes (2008) Proc. Natl. Acad. Sci. USA, 105, pp. 16653-16658; Roguev, A., Conservation and rewiring of functional modules revealed by an epistasis map in fssion yeast (2008) Science, 322, pp. 405-410; Babu, M., Systems-level approaches for identifying and analyzing genetic interaction networks in Escherichia coli and extensions to other prokaryotes (2009) Mol. Biosyst., 5, pp. 1439-1455; Leek, J.T., Tackling the widespread and critical impact of batch effects in high-throughput data (2010) Nat Rev. Genet., 11, pp. 733-739; He, X., Qian, W., Wang, Z., Li, Y., Zhang, J., Prevalent positive epistasis in Escherichia coli and Saccharomyces cerevisiae metabolic networks (2010) Nat Genet., 42, pp. 272-276; Hughes, T.R., Functional discovery via a compendium of expression profles (2000) Cell, 102, pp. 109-126; Jasnos, L., Korona, R., Epistatic buffering of ftness loss in yeast double deletion strains (2007) Nat Genet., 39, pp. 550-554; Warringer, J., Ericson, E., Fernandez, L., Nerman, O., Blomberg, A., High-resolution yeast phenomics resolves different physiological features in the saline response (2003) Proc. Natl. Acad. Sci. USA, 100, pp. 15724-15729; Brauer, M.J., Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast (2008) Mol. Biol. Cell, 19, pp. 352-367; Hartman, J.L.T., Tippery, N.P., Systematic quantifcation of gene interactions by phenotypic array analysis (2004) Genome Biol., 5, pp. R49; Friesen, H., Characterization of the yeast amphiphysins Rvs161p and Rvs167p reveals roles for the Rvs heterodimer in vivo (2006) Mol. Biol. Cell, 17, pp. 1306-1321; Bellaoui, M., Elg1 forms an alternative RFC complex important for DNA replication and genome integrity (2003) EMBO J., 22, pp. 4304-4313; Stark, C., BioGRID: A general repository for interaction datasets (2006) Nucleic Acids Res., 34, pp. D535-D539","Andrews, B.; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada; email: brenda.andrews@utoronto.ca",,,,,,,,15487091,,,10.1038/nmeth.1534,21076421,"English","Nat. Methods",Article,Scopus
"Demir E., Paley S., Fukuda K., Lemer C., Vastrik I., Wu G., D'Eustachio P., Schaefer C., Luciano J., Schacherer F., Martinez-Flores I., Hu Z., Jimenez-Jacinto V., Joshi-Tope G., Kandasamy K., Lopez-Fuentes A.C., Mi H., Pichler E., Rodchenkov I., Splendiani A., Tkachev S., Zucker J., Gopinath G., Rajasimha H., Ramakrishnan R., Shah I., Syed M., Anwar N., Babur O., Blinov M., Brauner E., Corwin D., Donaldson S., Gibbons F., Goldberg R., Hornbeck P., Luna A., Murray-Rust P., Neumann E., Reubenacker O., Samwald M., Van Iersel M., Wimalaratne S., Allen K., Braun B., Whirl-Carrillo M., Cheung K.-H., Dahlquist K., Finney A., Gillespie M., Glass E., Gong L., Haw R., Honig M., Hubaut O., Kane D., Krupa S., Kutmon M., Leonard J., Marks D., Merberg D., Petri V., Pico A., Ravenscroft D., Ren L., Shah N., Sunshine M., Tang R., Whaley R., Letovksy S., Buetow K.H., Rzhetsky A., Schachter V., Sobral B.S., Dogrusoz U., McWeeney S., Aladjem M., Birney E., Collado-Vides J., Goto S., Hucka M., Novere N.L., Maltsev N., Pandey A., Thomas P., Wingender E., Karp P.D., Sander C., Bader G.D.","Erratum: The BioPAX community standard for pathway data sharing (Nat. Biotechnol. (2010) 28 (935-942)",2010,"Nature Biotechnology",28,12,,1308,,,,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78650004198&partnerID=40&md5=70920375b4d64c8b1f17d5c4269da2d7",,"Demir, E.; Paley, S.; Fukuda, K.; Lemer, C.; Vastrik, I.; Wu, G.; D'Eustachio, P.; Schaefer, C.; Luciano, J.; Schacherer, F.; Martinez-Flores, I.; Hu, Z.; Jimenez-Jacinto, V.; Joshi-Tope, G.; Kandasamy, K.; Lopez-Fuentes, A.C.; Mi, H.; Pichler, E.; Rodchenkov, I.; Splendiani, A.; Tkachev, S.; Zucker, J.; Gopinath, G.; Rajasimha, H.; Ramakrishnan, R.; Shah, I.; Syed, M.; Anwar, N.; Babur, Ö.; Blinov, M.; Brauner, E.; Corwin, D.; Donaldson, S.; Gibbons, F.; Goldberg, R.; Hornbeck, P.; Luna, A.; Murray-Rust, P.; Neumann, E.; Reubenacker, O.; Samwald, M.; Van Iersel, M.; Wimalaratne, S.; Allen, K.; Braun, B.; Whirl-Carrillo, M.; Cheung, K.-H.; Dahlquist, K.; Finney, A.; Gillespie, M.; Glass, E.; Gong, L.; Haw, R.; Honig, M.; Hubaut, O.; Kane, D.; Krupa, S.; Kutmon, M.; Leonard, J.; Marks, D.; Merberg, D.; Petri, V.; Pico, A.; Ravenscroft, D.; Ren, L.; Shah, N.; Sunshine, M.; Tang, R.; Whaley, R.; Letovksy, S.; Buetow, K.H.; Rzhetsky, A.; Schachter, V.; Sobral, B.S.; Dogrusoz, U.; McWeeney, S.; Aladjem, M.; Birney, E.; Collado-Vides, J.; Goto, S.; Hucka, M.; Novère, N.L.; Maltsev, N.; Pandey, A.; Thomas, P.; Wingender, E.; Karp, P.D.; Sander, C.; Bader, G.D.",[No abstract available],,"erratum; error; priority journal",,,,,,,"Demir, E.",,,,,,,,10870156,,NABIF,10.1038/nbt1210-1308c,,"English","Nat. Biotechnol.",Erratum,Scopus
"Jain S., Bader G.D.","An improved method for scoring protein-protein interactions using semantic similarity within the gene ontology",2010,"BMC Bioinformatics",11,, 562,,,,22,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78149449890&partnerID=40&md5=e9703707613f33764ea8bd28ea001b47","Department of Computer Science, University of Toronto, 10 Kings College Road, Toronto, ON M5 S 3G4, Canada; Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5 S 3E1, Canada","Jain, S., Department of Computer Science, University of Toronto, 10 Kings College Road, Toronto, ON M5 S 3G4, Canada, Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5 S 3E1, Canada; Bader, G.D., Department of Computer Science, University of Toronto, 10 Kings College Road, Toronto, ON M5 S 3G4, Canada, Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, ON M5 S 3E1, Canada","Background: Semantic similarity measures are useful to assess the physiological relevance of protein-protein interactions (PPIs). They quantify similarity between proteins based on their function using annotation systems like the Gene Ontology (GO). Proteins that interact in the cell are likely to be in similar locations or involved in similar biological processes compared to proteins that do not interact. Thus the more semantically similar the gene function annotations are among the interacting proteins, more likely the interaction is physiologically relevant. However, most semantic similarity measures used for PPI confidence assessment do not consider the unequal depth of term hierarchies in different classes of cellular location, molecular function, and biological process ontologies of GO and thus may over-or under-estimate similarity.Results: We describe an improved algorithm, Topological Clustering Semantic Similarity (TCSS), to compute semantic similarity between GO terms annotated to proteins in interaction datasets. Our algorithm, considers unequal depth of biological knowledge representation in different branches of the GO graph. The central idea is to divide the GO graph into sub-graphs and score PPIs higher if participating proteins belong to the same sub-graph as compared to if they belong to different sub-graphs.Conclusions: The TCSS algorithm performs better than other semantic similarity measurement techniques that we evaluated in terms of their performance on distinguishing true from false protein interactions, and correlation with gene expression and protein families. We show an average improvement of 4.6 times the F1score over Resnik, the next best method, on our Saccharomyces cerevisiae PPI dataset and 2 times on our Homo sapiens PPI dataset using cellular component, biological process and molecular function GO annotations. © 2010 Jain and Bader; licensee BioMed Central Ltd.",,"Homo sapiens; Saccharomyces cerevisiae; protein; algorithm; article; chemistry; genetics; human; metabolism; methodology; molecular genetics; protein analysis; protein database; semantics; Algorithms; Databases, Protein; Humans; Molecular Sequence Annotation; Protein Interaction Mapping; Proteins; Semantics",,"protein, 67254-75-5; Proteins",,,,"Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Sherlock, G., Gene ontology: tool for the unification of biology. 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Faller, A.J., An Average Correlation Coefficient (1981) Journal of Applied Metereology, 20, pp. 203-205","Bader, G.D.; Department of Computer Science, University of Toronto, 10 Kings College Road, Toronto, ON M5 S 3G4, Canada; email: gary.bader@utoronto.ca",,,,,,,,14712105,,BBMIC,10.1186/1471-2105-11-562,21078182,"English","BMC Bioinform.",Article,Scopus
"Montojo J., Zuberi K., Rodriguez H., Kazi F., Wright G., Donaldson S.L., Morris Q., Bader G.D.","GeneMANIA cytoscape plugin: Fast gene function predictions on the desktop",2010,"Bioinformatics",26,22, btq562,2927,2928,,20,"http://www.scopus.com/inward/record.url?eid=2-s2.0-78149262301&partnerID=40&md5=5ba549251e0ed476753a70c990301356","Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada","Montojo, J., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Zuberi, K., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Rodriguez, H., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Kazi, F., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Wright, G., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Donaldson, S.L., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Morris, Q., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Bader, G.D., Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada","Summary: The GeneMANIA Cytoscape plugin brings fast gene function prediction capabilities to the desktop. GeneMANIA identifies the most related genes to a query gene set using a guilt-by-association approach. The plugin uses over 800 networks from six organisms and each related gene is traceable to the source network used to make the prediction. Users may add their own interaction networks and expression profile data to complement or override the default data. © The Author(s) 2010. Published by Oxford University Press.",,"algorithm; article; biology; computer program; factual database; gene; gene regulatory network; methodology; Algorithms; Computational Biology; Databases, Factual; Gene Regulatory Networks; Genes; Software",,,,,,"Barrett, T., NCBI GEO: archive for high-throughput functional genomic data (2009) Nucleic Acids Res., 37, pp. D885-D890; Breitkreutz, B.J., The BioGRID Interaction Database: 2008 update (2008) Nucleic Acids Res., 36, pp. D637-D640; Brown, K.R., Jurisica, I., Online predicted human interaction database (2005) Bioinformatics, 21, pp. 2076-2082; Harsha, H.C., A compendium of potential biomarkers of pancreatic cancer (2009) PLoS Med, 6, pp. e1000046; Mostafavi, S., Morris, Q., Fast integration of heterogeneous data sources for predicting gene function with limited annotation (2010) Bioinformatics, 26, pp. 1759-1765; Mostafavi, S., GeneMANIA: a real-time multiple association network integration algorithm for prediction gene function (2008) Genome Biol., 9, pp. S4; Pena-Castillo, L., A critical assessment of Mus musculus gene function prediction using integrated genomic evidence (2008) Genome Biol., 9, pp. S2; Shannon, P., Cytoscape: a software environment for integrated models of biomolecular interaaction networks (2003) Genome Res, 13, pp. 2498-2504; Warde-Farley, D., The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function (2010) Nucleic Acids Res., 38, pp. W214-W220","Morris, Q.; Banting and Best Department of Medical Research, Departments of Molecular Genetics and Computer Science, The Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; email: quaid.morris@utoronto.ca",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/btq562,20926419,"English","Bioinformatics",Article,Scopus
"Kirouac D.C., Ito C., Csaszar E., Roch A., Yu M., Sykes E.A., Bader G.D., Zandstra P.W.","Dynamic interaction networks in a hierarchically organized tissue",2010,"Molecular Systems Biology",6,, 417,,,,38,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77957762129&partnerID=40&md5=cf507a8c2bbec1d665274032ad6c2c7a","Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada; Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Department of Medical Genetics, University of Toronto, Toronto, ON, Canada; Department of Computer Science, University of Toronto, Toronto, ON, Canada; Samuel Luenfeld Research Institute, Joseph and Wolf Lebovic Health Complex, Mount Sinai Hospital, Toronto, ON, Canada; Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada; McEwen Centre for Regenerative Medicine, University Health Network, Toronto Medical Discovery Tower, Toronto, ON, Canada; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States","Kirouac, D.C., Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States; Ito, C., Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Csaszar, E., Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada; Roch, A., Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Yu, M., Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Sykes, E.A., Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Bader, G.D., Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Medical Genetics, University of Toronto, Toronto, ON, Canada, Department of Computer Science, University of Toronto, Toronto, ON, Canada, Samuel Luenfeld Research Institute, Joseph and Wolf Lebovic Health Complex, Mount Sinai Hospital, Toronto, ON, Canada; Zandstra, P.W., Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada, McEwen Centre for Regenerative Medicine, University Health Network, Toronto Medical Discovery Tower, Toronto, ON, Canada","Intercellular (between cell) communication networks maintain homeostasis and coordinate regenerative and developmental cues in multicellular organisms. Despite the importance of intercellular networks in stem cell biology, their rules, structure and molecular components are poorly understood. Herein, we describe the structure and dynamics of intercellular and intracellular networks in a stem cell derived, hierarchically organized tissue using experimental and theoretical analyses of cultured human umbilical cord blood progenitors. By integrating high-throughput molecular profiling, database and literature mining, mechanistic modeling, and cell culture experiments, we show that secreted factor-mediated intercellular communication networks regulate blood stem cell fate decisions. In particular, self-renewal is modulated by a coupled positiveĝ€""negative intercellular feedback circuit composed of megakaryocyte-derived stimulatory growth factors (VEGF, PDGF, EGF, and serotonin) versus monocyte-derived inhibitory factors (CCL3, CCL4, CXCL10, TGFB2, and TNFSF9). We reconstruct a stem cell intracellular network, and identify PI3K, Raf, Akt, and PLC as functionally distinct signal integration nodes, linking extracellular, and intracellular signaling. This represents the first systematic characterization of how stem cell fate decisions are regulated non-autonomously through lineage-specific interactions with differentiated progeny. © 2010 EMBO and Macmillan Publishers Limited. All rights reserved.","cellular networks; hematopoiesis; intercellular signaling; self-renewal; stem cells","epidermal growth factor; gamma interferon inducible protein 10; macrophage inflammatory protein 1alpha; macrophage inflammatory protein 1beta; platelet derived growth factor; protein; protein TNFSF9; serotonin; transforming growth factor beta2; unclassified drug; vasculotropin; signal peptide; article; cell communication; cell fate; cell population; controlled study; feedback system; gene expression; genome; hematopoietic stem cell; human; human cell; human cell culture; in vitro study; priority journal; simulation; stem cell; stem cell expansion; theory; umbilical cord blood; analysis of variance; biological model; biology; cell communication; cell culture; cell differentiation; cluster analysis; computer simulation; cytology; data mining; fetus blood; gene expression profiling; gene regulatory network; hematopoietic stem cell; methodology; physiology; signal transduction; statistical model; Analysis of Variance; Cell Communication; Cell Differentiation; Cells, Cultured; Cluster Analysis; Computational Biology; Computer Simulation; Data Mining; Fetal Blood; Gene Expression Profiling; Gene Regulatory Networks; Hematopoietic Stem Cells; Humans; Intercellular Signaling Peptides and Proteins; Linear Models; Models, Biological; Signal Transduction",,"epidermal growth factor, 62229-50-9; gamma interferon inducible protein 10, 97741-20-3; macrophage inflammatory protein 1alpha, 155075-84-6; macrophage inflammatory protein 1beta, 122071-81-2; protein, 67254-75-5; serotonin, 50-67-9; vasculotropin, 127464-60-2; Intercellular Signaling Peptides and Proteins",,,,"Bamborough, P., Drewry, D., Harper, G., Smith, G.K., Schneider, K., Assessment of chemical coverage of kinome space and its implications for kinase drug discovery (2008) JMed Chem, 51, pp. 7898-7914; Brown, K.R., Jurisica, I., Online predicted human interaction database (2005) Bioinformatics, 21, pp. 2076-2082; Broxmeyer, H.E., Kim, C.H., Regulation of hematopoiesis in a sea of chemokine family members with a plethora of redundant activities (1999) Exp Hematol, 27, pp. 1113-1123; Bryder, D., Ramsfjell, V., Dybedal, I., Theilgaard-Monch, K., Hogerkorp, C.M., Adolfsson, J., Borge, O.J., Jacobsen, S.E., Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation (2001) JExpMed, 194, pp. 941-952; Cashman, J.D., Eaves, A.C., Raines, E.W., Ross, R., Eaves, C.J., Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. I. 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Yang, H., Robinson, S.N., Lu, J., Decker, W.K., Xing, D., Steiner, D., Parmar, S., Shpall, E.J., CD3(+) and/or CD14(+ ) depletion from cord blood mononuclear cells before ex vivo expansion culture improves total nucleated cell and CD34(+) cell yields (2010) Bone Marrow Transplant, 45, pp. 1000-1007; Yang, M., Srikiatkhachorn, A., Anthony, M., Chesterman, C.N., Chong, B.H., Serotonin uptake, storage and metabolism in megakaryoblasts (1996) IntJHematol, 63, pp. 137-142","Zandstra, P. W.; Terrence Donnelly Centre for Cellular and Biomolecular Research, Institute for Biomaterials and Biomedical Engineering, 160 College Street, Toronto, ON M5S 3E1, Canada; email: peter.zandstra@utoronto.ca",,,,,,,,17444292,,,10.1038/msb.2010.71,20924352,"English","Mol. Syst. Biol.",Article,Scopus
"Hui S., Bader G.D.","Proteome scanning to predict PDZ domain interactions using support vector machines",2010,"BMC Bioinformatics",11,, 507,,,,18,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77957737014&partnerID=40&md5=1c0c2b0e539551ffafe050b523ddfb03","Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto ON, Canada","Hui, S., Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto ON, Canada; Bader, G.D., Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto ON, Canada","Background: PDZ domains mediate protein-protein interactions involved in important biological processes through the recognition of short linear motifs in their target proteins. Two recent independent studies have used protein microarray or phage display technology to detect PDZ domain interactions with peptide ligands on a large scale. Several computational predictors of PDZ domain interactions have been developed, however they are trained using only protein microarray data and focus on limited subsets of PDZ domains. An accurate predictor of genomic PDZ domain interactions would allow the proteomes of organisms to be scanned for potential binders. Such an application would require an accurate and precise predictor to avoid generating too many false positive hits given the large amount of possible interactors in a given proteome. Once validated these predictions will help to increase the coverage of current PDZ domain interaction networks and further our understanding of the roles that PDZ domains play in a variety of biological processes.Results: We developed a PDZ domain interaction predictor using a support vector machine (SVM) trained with both protein microarray and phage display data. In order to use the phage display data for training, which only contains positive interactions, we developed a method to generate artificial negative interactions. Using cross-validation and a series of independent tests, we showed that our SVM successfully predicts interactions in different organisms. We then used the SVM to scan the proteomes of human, worm and fly to predict binders for several PDZ domains. Predictions were validated using known genomic interactions and published protein microarray experiments. Based on our results, new protein interactions potentially associated with Usher and Bardet-Biedl syndromes were predicted. A comparison of performance measures (F1 measure and FPR) for the SVM and published predictors demonstrated our SVM's improved accuracy and precision at proteome scanning.Conclusions: We built an SVM using mouse and human experimental training data to predict PDZ domain interactions. We showed that it correctly predicts known interactions from proteomes of different organisms and is more accurate and precise at proteome scanning compared with published state-of-the-art predictors. © 2010 Hui and Bader; licensee BioMed Central Ltd.",,"protein; proteome; animal; article; artificial intelligence; binding site; chemistry; human; metabolism; methodology; mouse; PDZ domain; protein analysis; protein microarray; Animals; Artificial Intelligence; Binding Sites; Humans; Mice; PDZ Domains; Protein Array Analysis; Protein Interaction Mapping; Proteins; Proteome",,"protein, 67254-75-5; Proteins; Proteome",,,,"Ponting, C.P., Evidence for PDZ domains in bacteria, yeast, and plants (1997) Protein Sci, 6, pp. 464-468. , 10.1002/pro.5560060225, 2143646, 9041651; Pawson, T., Nash, P., Assembly of cell regulatory systems through protein interaction domains (2003) Science, 300, pp. 445-452. , 10.1126/science.1083653, 12702867; Dev, K.K., Making protein interactions druggable: targeting PDZ domains (2004) Nat Rev Drug Discov, 3, pp. 1047-1056. , 10.1038/nrd1578, 15573103; 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Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto ON, Canada; email: gary.bader@utoronto.ca",,,,,,,,14712105,,BBMIC,10.1186/1471-2105-11-507,20939902,"English","BMC Bioinform.",Article,Scopus
"Ernst A., Gfeller D., Kan Z., Seshagiri S., Kim P.M., Bader G.D., Sidhu S.S.","Coevolution of PDZ domain-ligand interactions analyzed by high-throughput phage display and deep sequencing",2010,"Molecular BioSystems",6,10,,1782,1790,,24,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77956544553&partnerID=40&md5=729680703c7eb445404c1975e3aefae7","Department of Molecular Genetics, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States","Ernst, A., Department of Molecular Genetics, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Gfeller, D., Department of Molecular Genetics, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Kan, Z., Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; Seshagiri, S., Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; Kim, P.M., Department of Molecular Genetics, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Bader, G.D., Department of Molecular Genetics, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Sidhu, S.S., Department of Molecular Genetics, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","The determinants of binding specificities of peptide recognition domains and their evolution remain important problems in molecular systems biology. Here, we present a new methodology to analyze the coevolution between a domain and its ligands by combining high-throughput phage display with deep sequencing. First, from a library of PDZ domains with diversity introduced at ten positions in the binding site, we evolved domains for binding to 15 distinct peptide ligands. Interestingly, for a given peptide many different functional domains emerged, which exhibited only limited sequence homology, showing that many different binding sites can recognize a given peptide. Subsequently, we used peptide-phage libraries and deep sequencing to map the specificity profiles of these evolved domains at high resolution, and we found that the domains recognize their cognate peptides with high affinity but low specificity. Our analysis reveals two aspects of evolution of new binding specificities. First, we were able to identify some common features amongst domains raised against a common peptide. 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"Demir E., Cary M.P., Paley S., Fukuda K., Lemer C., Vastrik I., Wu G., D'Eustachio P., Schaefer C., Luciano J., Schacherer F., Martinez-Flores I., Hu Z., Jimenez-Jacinto V., Joshi-Tope G., Kandasamy K., Lopez-Fuentes A.C., Mi H., Pichler E., Rodchenkov I., Splendiani A., Tkachev S., Zucker J., Gopinath G., Rajasimha H., Ramakrishnan R., Shah I., Syed M., Anwar N., Babur O., Blinov M., Brauner E., Corwin D., Donaldson S., Gibbons F., Goldberg R., Hornbeck P., Luna A., Murray-Rust P., Neumann E., Reubenacker O., Samwald M., Van Iersel M., Wimalaratne S., Allen K., Braun B., Whirl-Carrillo M., Cheung K.-H., Dahlquist K., Finney A., Gillespie M., Glass E., Gong L., Haw R., Honig M., Hubaut O., Kane D., Krupa S., Kutmon M., Leonard J., Marks D., Merberg D., Petri V., Pico A., Ravenscroft D., Ren L., Shah N., Sunshine M., Tang R., Whaley R., Letovksy S., Buetow K.H., Rzhetsky A., Schachter V., Sobral B.S., Dogrusoz U., McWeeney S., Aladjem M., Birney E., Collado-Vides J., Goto S., Hucka M., Novere N.L., Maltsev N., Pandey A., Thomas P., Wingender E., Karp P.D., Sander C., Bader G.D.","The BioPAX community standard for pathway data sharing",2010,"Nature Biotechnology",28,9,,935,942,,104,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77956664073&partnerID=40&md5=212cd8f873469c478944ad66c090215a","Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Center for Bioinformatics, Computer Engineering Department, Bilkent University, Ankara, Turkey; SRI International, Menlo Park, CA, United States; Institute for Bioinformatics Research and Development, Japan Science and Technology Agency, Tokyo, Japan; Université Libre de Bruxelles, Bruxelles, Belgium; European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom; Ontario Institute for Cancer Research, Toronto, ON, Canada; NYU School of Medicine, New York, NY, United States; National Cancer Institute, Center for Biomedical Informatics and Information Technology, Rockville, MD, United States; Predictive Medicine, Belmont, MA, United States; BIOBASE Corporation, Beverly, MA, United States; Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico; Biomolecular Systems Laboratory, Boston University, Boston, MA, United States; Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States; McKusick-Nathans Institute of Genetic Medicine, Departments of Biological Chemistry, Pathology and Oncology, Johns Hopkins University, Baltimore, MD, United States; Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico; Artificial Intelligence Center, SRI International, Menlo Park, CA, United States; Donnelly Center for Cellular and Biomolecular Research, Banting, Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Faculté de Médecine, Université Rennes 1, Rennes, France; Rothamsted Research, Harpenden, United Kingdom; Cell Signaling Technology, Inc., Danvers, MA, United States; Broad Institute, Cambridge, MA, United States; Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, United States; Virginia Bioinformatics Institute, Virginia Polytechnic Institute, State University, Blacksburg, VA, United States; Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States; Department of Behavioral Neuroscience. Oregon Health, Science University, Portland, OR, United States; US Environmental Protection Agency, Durham, NC, United States; Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, United States; University of Connecticut Health Center, Farmington, CT, United States; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, United States; Lexikos Corporation, Boston, MA, United States; Biotechnology Division, National Institute of Standards and Technology, Gaithersburg, MD, United States; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; Unilever Centre for Molecular Sciences Informatics, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom; Clinical Semantics Group, Lexington, MA, United States; Center for Cell Analysis and Modeling, University of Connecticut Health Center, Storrs, CT, United States; Digital Enterprise Research Institute, National University of Ireland, Galway, Ireland; Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria; Department of Bioinformatics, Maastricht University, Maastricht, Netherlands; University of Auckland, Auckland, New Zealand; Syngenta Biotech Inc., Research Triangle Park, NC, United States; Department of Genetics, Stanford University, Stanford, CA, United States; Yale Center for Medical Informatics, Yale University, New Haven, CT, United States; Loyola Marymount University, Los Angeles, CA, United States; Physiomics PLC, Magdalen Centre, Oxford Science Park, Oxford, United Kingdom; St. John's University, Jamaica, NY, United States; Columbia University, New York, NY, United States; SRA International, Fairfax, VA, United States; Novartis Knowledge Center, Cambridge, MA, United States; University of Ottawa, Ottawa, ON, Canada; Department of Systems Biology, Harvard Medical School, Boston, MA, United States; Vertex Pharmaceuticals, Cambridge, MA, United States; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, United States; Gladstone Institute of Cardiovascular Disease, San Francisco, CA, United States; Department of Plant Breeding and Genetics, Cornell University, Ithaca, NY, United States; Centre for Biomedical Informatics, School of Medicine, Stanford University, Stanford, CA, United States; Computational Sciences, Informatics, Millennium Pharmaceuticals Inc., Cambridge, MA, United States; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD, United States; Institute for Genomics and Systems Biology, University of Chicago and Argonne National Laboratory, Chicago, IL, United States; Total Gas and Power, Paris, France; Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan; Biological Network Modeling Center, California Institute of Technology, Pasadena, CA, United States; Department of Bioinformatics, Göttingen, Germany","Demir, E., Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, Center for Bioinformatics, Computer Engineering Department, Bilkent University, Ankara, Turkey; Cary, M.P., Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Paley, S., SRI International, Menlo Park, CA, United States; Fukuda, K., Institute for Bioinformatics Research and Development, Japan Science and Technology Agency, Tokyo, Japan; Lemer, C., Université Libre de Bruxelles, Bruxelles, Belgium; Vastrik, I., European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom; Wu, G., Ontario Institute for Cancer Research, Toronto, ON, Canada; D'Eustachio, P., NYU School of Medicine, New York, NY, United States; Schaefer, C., National Cancer Institute, Center for Biomedical Informatics and Information Technology, Rockville, MD, United States; Luciano, J., Predictive Medicine, Belmont, MA, United States; Schacherer, F., BIOBASE Corporation, Beverly, MA, United States; Martinez-Flores, I., Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico; Hu, Z., Biomolecular Systems Laboratory, Boston University, Boston, MA, United States; Jimenez-Jacinto, V., Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico; Joshi-Tope, G., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States; Kandasamy, K., McKusick-Nathans Institute of Genetic Medicine, Departments of Biological Chemistry, Pathology and Oncology, Johns Hopkins University, Baltimore, MD, United States; Lopez-Fuentes, A.C., Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico; Mi, H., Artificial Intelligence Center, SRI International, Menlo Park, CA, United States; Pichler, E.; Rodchenkov, I., Donnelly Center for Cellular and Biomolecular Research, Banting, Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Splendiani, A., Faculté de Médecine, Université Rennes 1, Rennes, France, Rothamsted Research, Harpenden, United Kingdom; Tkachev, S., Cell Signaling Technology, Inc., Danvers, MA, United States; Zucker, J., Broad Institute, Cambridge, MA, United States; Gopinath, G., Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, United States; Rajasimha, H., Virginia Bioinformatics Institute, Virginia Polytechnic Institute, State University, Blacksburg, VA, United States, Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States; Ramakrishnan, R., Department of Behavioral Neuroscience. Oregon Health, Science University, Portland, OR, United States; Shah, I., US Environmental Protection Agency, Durham, NC, United States; Syed, M., Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, United States; Anwar, N., Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Babur, Ö., Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, Center for Bioinformatics, Computer Engineering Department, Bilkent University, Ankara, Turkey; Blinov, M., University of Connecticut Health Center, Farmington, CT, United States; Brauner, E., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, United States; Corwin, D., Lexikos Corporation, Boston, MA, United States; Donaldson, S., Donnelly Center for Cellular and Biomolecular Research, Banting, Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Gibbons, F., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, United States; Goldberg, R., Biotechnology Division, National Institute of Standards and Technology, Gaithersburg, MD, United States; Hornbeck, P., Cell Signaling Technology, Inc., Danvers, MA, United States; Luna, A., Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; Murray-Rust, P., Unilever Centre for Molecular Sciences Informatics, Department of Chemistry, University of Cambridge, Cambridge, United Kingdom; Neumann, E., Clinical Semantics Group, Lexington, MA, United States; Reubenacker, O., Center for Cell Analysis and Modeling, University of Connecticut Health Center, Storrs, CT, United States; Samwald, M., Digital Enterprise Research Institute, National University of Ireland, Galway, Ireland, Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria; Van Iersel, M., Department of Bioinformatics, Maastricht University, Maastricht, Netherlands; Wimalaratne, S., University of Auckland, Auckland, New Zealand; Allen, K., Syngenta Biotech Inc., Research Triangle Park, NC, United States; Braun, B., BIOBASE Corporation, Beverly, MA, United States; Whirl-Carrillo, M., Department of Genetics, Stanford University, Stanford, CA, United States; Cheung, K.-H., Yale Center for Medical Informatics, Yale University, New Haven, CT, United States; Dahlquist, K., Loyola Marymount University, Los Angeles, CA, United States; Finney, A., Physiomics PLC, Magdalen Centre, Oxford Science Park, Oxford, United Kingdom; Gillespie, M., St. John's University, Jamaica, NY, United States; Glass, E., Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, United States; Gong, L., Department of Genetics, Stanford University, Stanford, CA, United States; Haw, R., Ontario Institute for Cancer Research, Toronto, ON, Canada; Honig, M., Columbia University, New York, NY, United States; Hubaut, O., Université Libre de Bruxelles, Bruxelles, Belgium; Kane, D., SRA International, Fairfax, VA, United States; Krupa, S., Novartis Knowledge Center, Cambridge, MA, United States; Kutmon, M., University of Ottawa, Ottawa, ON, Canada; Leonard, J., Syngenta Biotech Inc., Research Triangle Park, NC, United States; Marks, D., Department of Systems Biology, Harvard Medical School, Boston, MA, United States; Merberg, D., Vertex Pharmaceuticals, Cambridge, MA, United States; Petri, V., Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, United States; Pico, A., Gladstone Institute of Cardiovascular Disease, San Francisco, CA, United States; Ravenscroft, D., Department of Plant Breeding and Genetics, Cornell University, Ithaca, NY, United States; Ren, L., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States; Shah, N., Centre for Biomedical Informatics, School of Medicine, Stanford University, Stanford, CA, United States; Sunshine, M., Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; Tang, R., Syngenta Biotech Inc., Research Triangle Park, NC, United States; Whaley, R., Syngenta Biotech Inc., Research Triangle Park, NC, United States; Letovksy, S., Computational Sciences, Informatics, Millennium Pharmaceuticals Inc., Cambridge, MA, United States; Buetow, K.H., Center for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD, United States; Rzhetsky, A., Institute for Genomics and Systems Biology, University of Chicago and Argonne National Laboratory, Chicago, IL, United States; Schachter, V., Total Gas and Power, Paris, France; Sobral, B.S., Virginia Bioinformatics Institute, Virginia Polytechnic Institute, State University, Blacksburg, VA, United States; Dogrusoz, U., Center for Bioinformatics, Computer Engineering Department, Bilkent University, Ankara, Turkey; McWeeney, S., Department of Behavioral Neuroscience. Oregon Health, Science University, Portland, OR, United States; Aladjem, M., Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States; Birney, E., European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom; Collado-Vides, J., Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico; Goto, S., Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan; Hucka, M., Biological Network Modeling Center, California Institute of Technology, Pasadena, CA, United States; Novère, N.L., European Bioinformatics Institute, Hinxton, Cambridge, United Kingdom; Maltsev, N., Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, United States; Pandey, A., McKusick-Nathans Institute of Genetic Medicine, Departments of Biological Chemistry, Pathology and Oncology, Johns Hopkins University, Baltimore, MD, United States; Thomas, P., Artificial Intelligence Center, SRI International, Menlo Park, CA, United States; Wingender, E., Department of Bioinformatics, Göttingen, Germany; Karp, P.D., SRI International, Menlo Park, CA, United States; Sander, C., Computational Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Bader, G.D., Donnelly Center for Cellular and Biomolecular Research, Banting, Best Department of Medical Research, University of Toronto, Toronto, ON, Canada","Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery. © 2010 Nature America, Inc. 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McIlraith, S.A., Dimitris Plexousakis, D. & van Harmelen, F.) 229\-243, Springer; Sowa, J.F., (2000) Knowledge Representation: Logical, Philosophical, and Computational Foundations, , (Brooks/Cole); Wheeler, D.L., Database resources of the National Center for Biotechnology Information (2007) Nucleic Acids Res., 35, pp. D5-D12","Bader, G. D.; Donnelly Center for Cellular and Biomolecular Research, Banting, Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; email: biopax-paper@biopax.org",,,,,,,,10870156,,NABIF,10.1038/nbt.1666,20829833,"English","Nat. Biotechnol.",Review,Scopus
"Lopes C.T., Franz M., Kazi F., Donaldson S.L., Morris Q., Bader G.D.","Cytoscape web: An interactive web-based network browser",2010,"Bioinformatics",26,18, btq430,2347,2348,,89,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77956548953&partnerID=40&md5=fa81dd2115800a7db7bda3af64d687da","Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","Lopes, C.T., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Franz, M., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Kazi, F., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Donaldson, S.L., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Morris, Q., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Bader, G.D., Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","Summary: Cytoscape Web is a web-based network visualization tool-modeled after Cytoscape-which is open source, interactive, customizable and easily integrated into web sites. Multiple file exchange formats can be used to load data into Cytoscape Web, including GraphML, XGMML and SIF. © The Author(s) 2010. Published by Oxford University Press.",,"article; computer program; Internet; Internet; Software",,,,,,"Hooper, S.D., Bork, P., Medusa: a simple tool for interaction graph analysis (2005) Bioinformatics, 21, pp. 4432-4433; Jensen, L.J., STRING 8-a global view on proteins and their functional interactions in 630 organisms (2009) Nucleic Acids Res., 37, pp. D412-D416; Klammer, M., jSquid: a Java applet for graphical on-line network exploration (2008) Bioinformatics, 24, pp. 1467-1468; Razick, S., iRefIndex: a consolidated protein interactions database with provenance (2008) BMC Bioinformatics, 9, p. 405; Shannon, P., Cytoscape: a software environment for integrated models of biomolecular interaction networks (2003) Genome Res., 13, pp. 2498-2504; Warde-Farley, D., The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function (2010) Nucleic Acids Res., 38, pp. W214-W220","Bader, G.D.; Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; email: gary.bader@utoronto.ca",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/btq430,20656902,"English","Bioinformatics",Article,Scopus
"Pinto D., Pagnamenta A.T., Klei L., Anney R., Merico D., Regan R., Conroy J., Magalhaes T.R., Correia C., Abrahams B.S., Almeida J., Bacchelli E., Bader G.D., Bailey A.J., Baird G., Battaglia A., Berney T., Bolshakova N., Bolte S., Bolton P.F., Bourgeron T., Brennan S., Brian J., Bryson S.E., Carson A.R., Casallo G., Casey J., Chung B.H.Y., Cochrane L., Corsello C., Crawford E.L., Crossett A., Cytrynbaum C., Dawson G., De Jonge M., Delorme R., Drmic I., Duketis E., Duque F., Estes A., Farrar P., Fernandez B.A., Folstein S.E., Fombonne E., Freitag C.M., Gilbert J., Gillberg C., Glessner J.T., Goldberg J., Green A., Green J., Guter S.J., Hakonarson H., Heron E.A., Hill M., Holt R., Howe J.L., Hughes G., Hus V., Igliozzi R., Kim C., Klauck S.M., Kolevzon A., Korvatska O., Kustanovich V., Lajonchere C.M., Lamb J.A., Laskawiec M., Leboyer M., Le Couteur A., Leventhal B.L., Lionel A.C., Liu X.-Q., Lord C., Lotspeich L., Lund S.C., Maestrini E., Mahoney W., Mantoulan C., Marshall C.R., McConachie H., McDougle C.J., McGrath J., McMahon W.M., Merikangas A., Migita O., Minshew N.J., Mirza G.K., Munson J., Nelson S.F., Noakes C., Noor A., Nygren G., Oliveira G., Papanikolaou K., Parr J.R., Parrini B., Paton T., Pickles A., Pilorge M., Piven J., Ponting C.P., Posey D.J., Poustka A., Poustka F., Prasad A., Ragoussis J., Renshaw K., Rickaby J., Roberts W., Roeder K., Roge B., Rutter M.L., Bierut L.J., Rice J.P., Salt J., Sansom K., Sato D., Segurado R., Sequeira A.F., Senman L., Shah N., Sheffield V.C., Soorya L., Sousa I., Stein O., Sykes N., Stoppioni V., Strawbridge C., Tancredi R., Tansey K., Thiruvahindrapduram B., Thompson A.P., Thomson S., Tryfon A., Tsiantis J., Van Engeland H., Vincent J.B., Volkmar F., Wallace S., Wang K., Wang Z., Wassink T.H., Webber C., Weksberg R., Wing K., Wittemeyer K., Wood S., Wu J., Yaspan B.L., Zurawiecki D., Zwaigenbaum L., Buxbaum J.D., Cantor R.M., Cook E.H., Coon H., Cuccaro M.L., Devlin B., Ennis S., Gallagher L., Geschwind D.H., Gill M., Haines J.L., Hallmayer J., Miller J., Monaco A.P., Nurnberger Jr J.I., Paterson A.D., Pericak-Vance M.A., Schellenberg G.D., Szatmari P., Vicente A.M., Vieland V.J., Wijsman E.M., Scherer S.W., Sutcliffe J.S., Betancur C.","Functional impact of global rare copy number variation in autism spectrum disorders",2010,"Nature",466,7304,,368,372,,427,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77954657070&partnerID=40&md5=89def4e563a08a462cef3ce9aecd793f","Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; School of Medicine, Medical Science University College, Dublin 4, Iran; Instituto Nacional de Saude Dr Ricardo Jorge 1649-016 Lisbon, Instituto Gulbenkian de Cîencia, 2780-156 Oeiras, Portugal; BioFIG-Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, C2.2.12, Campo Grande, 1749-016 Lisboa, Portugal; Department of Neurology and Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Hospital Pediátrico de Coimbra, 3000 - 076 Coimbra, Portugal; Department of Biology, University of Bologna, 40126 Bologna, Italy; Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford OX3 7JX, United Kingdom; Newcomen Centre, Guys Hospital, London SE1 9RT, United Kingdom; Stella Maris Institute for Child and Adolescent Neuropsychiatry, 56128 Calambrone (Pisa), Italy; Child and Adolescent Mental Health, University of Newcastle, Sir James Spence Institute, Newcastle upon Tyne NE1 4LP, United Kingdom; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, J.W. Goethe University Frankfurt, 60528 Frankfurt, Germany; Department of Child and Adolescent Psychiatry, Institute of Psychiatry, London SE5 8AF, United Kingdom; Human Genetics and Cognitive Functions, Institut Pasteur, University Paris Diderot-Paris 7, 75015 Paris, France; Autism Research Unit, Hospital for Sick Children and Bloorview Kids Rehab, University of Toronto, Toronto, ON M5G 1X8, Canada; Department of Pediatrics and Psychology, Dalhousie University, Halifax, NS B3K 6R8, Canada; Autism and Communicative Disorders Centre, University of Michigan, Ann Arbor, MI 48109-2054, United States; Department of Molecular Physiology and Biophysics, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN 37232, United States; Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Autism Speaks, NY 10016, United States; Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599-3366, United States; Department of Child Psychiatry, University Medical Center, Utrecht 3508 GA, Netherlands; INSERM U 955, APHP, Hôpital Robert Debré, Child and Adolescent Psychiatry, 75019 Paris, France; Department of Speech and Hearing Sciences, University of Washington, Seattle, WA 98195, United States; Disciplines of Genetics and Medicine, Memorial University of Newfoundland, St Johns, NL A1B 3V6, Canada; John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33101, United States; Division of Psychiatry, McGill University, Montreal, QC H3A 1A1, Canada; Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg S41345, Sweden; Center for Applied Genomics, Division of Human Genetics, Childrens Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8N 3Z5, Canada; Academic Department of Child Psychiatry, Booth Hall of Childrens Hospital, Blackley, Manchester M9 7AA, United Kingdom; Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, United States; Department of Pediatrics, Childrens Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States; Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of Medicine, NY 10029, United States; Department of Medicine, University of Washington, Seattle, WA 98195, United States; Autism Genetic Resource Exchange, Autism Speaks, Los Angeles, CA 90036-4234, United States; Centre for Integrated Genomic Medical Research, University of Manchester, Manchester M13 9PT, United Kingdom; Department of Psychiatry, Groupe Hospitalier Henri Mondor-Albert Chenevier, University Paris 12, Créteil 94000, France; Nathan Kline Institute for Psychiatric Research (NKI), 140 Old Orangeburg Road, Orangeburg, NY 10962, United States; Department of Child and Adolescent Psychiatry, New York University and NYU Child Study Center, 550 First Avenue, New York, NY 10016, United States; Department of Psychiatry, Division of Child and Adolescent Psychiatry and Child Development, Stanford University School of Medicine, Stanford, CA 94304, United States; Department of Pediatrics, McMaster University, Hamilton, ON L8N 3Z5, Canada; Centre DEudes et de Recherches en Psychopathologie, University de Toulouse le Mirail, Toulouse 31200, France; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, United States; Psychiatry Department, University of Utah Medical School, Salt Lake City, UT 84108, United States; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Department of Psychiatry and Behavioural Sciences, University of Washington, Seattle, WA 98195, United States; Department of Human Genetics, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, United States; Centre for Addiction and Mental Health, Clarke Institute and Department of Psychiatry, University of Toronto, Toronto, ON M5G 1X8, Canada; University Department of Child Psychiatry, Agia Sophia Childrens Hospital, Athens University, 115 27 Athens, Greece; Insitutes of Neuroscience and Health and Society, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom; Department of Medicine, School of Epidemiology and Health Science, University of Manchester, Manchester M13 9PT, United Kingdom; INSERM U952, CNRS UMR 7224, UPMC Univ Paris 06, Paris 75005, France; Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC 27599-3366, United States; MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London SE5 8AF, United Kingdom; Department of Psychiatry, Washington University in St Louis, School of Medicine, St Louis, MO 63130, United States; Department of Pediatrics, Howard Hughes Medical Institute Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States; Battelle Center for Mathematical Medicine, Research Institute at Nationwide Childrens Hospital, Ohio State University, Columbus, OH 43205, United States; Neuropsichiatria Infantile, Ospedale Santa Croce, 61032 Fano, Italy; Child Study Centre, Yale University, New Haven, CT 06520, United States; Department of Psychiatry, Carver College of Medicine, Iowa City, IA 52242, United States; Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2J3, Canada; Center for Human Genetics Research, Vanderbilt University Medical Centre, Nashville, TN 37232, United States; Pathology and Laboratory Medicine, University of Pennsylvania, PA 19104, United States; Departments of Biostatistics and Medicine, University of Washington, Seattle, WA 98195, United States; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada","Pinto, D., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Pagnamenta, A.T., Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; Klei, L., Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Anney, R., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Merico, D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Regan, R., School of Medicine, Medical Science University College, Dublin 4, Iran; Conroy, J., School of Medicine, Medical Science University College, Dublin 4, Iran; Magalhaes, T.R., Instituto Nacional de Saude Dr Ricardo Jorge 1649-016 Lisbon, Instituto Gulbenkian de Cîencia, 2780-156 Oeiras, Portugal, BioFIG-Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, C2.2.12, Campo Grande, 1749-016 Lisboa, Portugal; Correia, C., Instituto Nacional de Saude Dr Ricardo Jorge 1649-016 Lisbon, Instituto Gulbenkian de Cîencia, 2780-156 Oeiras, Portugal, BioFIG-Center for Biodiversity, Functional and Integrative Genomics, Campus da FCUL, C2.2.12, Campo Grande, 1749-016 Lisboa, Portugal; Abrahams, B.S., Department of Neurology and Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Almeida, J., Hospital Pediátrico de Coimbra, 3000 - 076 Coimbra, Portugal; Bacchelli, E., Department of Biology, University of Bologna, 40126 Bologna, Italy; Bader, G.D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada; Bailey, A.J., Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford OX3 7JX, United Kingdom; Baird, G., Newcomen Centre, Guys Hospital, London SE1 9RT, United Kingdom; Battaglia, A., Stella Maris Institute for Child and Adolescent Neuropsychiatry, 56128 Calambrone (Pisa), Italy; Berney, T., Child and Adolescent Mental Health, University of Newcastle, Sir James Spence Institute, Newcastle upon Tyne NE1 4LP, United Kingdom, Insitutes of Neuroscience and Health and Society, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom; Bolshakova, N., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Bölte, S., Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, J.W. Goethe University Frankfurt, 60528 Frankfurt, Germany; Bolton, P.F., Department of Child and Adolescent Psychiatry, Institute of Psychiatry, London SE5 8AF, United Kingdom; Bourgeron, T., Human Genetics and Cognitive Functions, Institut Pasteur, University Paris Diderot-Paris 7, 75015 Paris, France; Brennan, S., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Brian, J., Autism Research Unit, Hospital for Sick Children and Bloorview Kids Rehab, University of Toronto, Toronto, ON M5G 1X8, Canada; Bryson, S.E., Department of Pediatrics and Psychology, Dalhousie University, Halifax, NS B3K 6R8, Canada; Carson, A.R., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Casallo, G., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Casey, J., School of Medicine, Medical Science University College, Dublin 4, Iran; Chung, B.H.Y., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Cochrane, L., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Corsello, C., Autism and Communicative Disorders Centre, University of Michigan, Ann Arbor, MI 48109-2054, United States; Crawford, E.L., Department of Molecular Physiology and Biophysics, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN 37232, United States; Crossett, A., Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213, United States; Cytrynbaum, C., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Dawson, G., Autism Speaks, NY 10016, United States; De Jonge, M., Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599-3366, United States; Delorme, R., Department of Child Psychiatry, University Medical Center, Utrecht 3508 GA, Netherlands; Drmic, I., INSERM U 955, APHP, Hôpital Robert Debré, Child and Adolescent Psychiatry, 75019 Paris, France; Duketis, E., Autism Research Unit, Hospital for Sick Children and Bloorview Kids Rehab, University of Toronto, Toronto, ON M5G 1X8, Canada; Duque, F., Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, J.W. Goethe University Frankfurt, 60528 Frankfurt, Germany; Estes, A., Hospital Pediátrico de Coimbra, 3000 - 076 Coimbra, Portugal; Farrar, P., Department of Speech and Hearing Sciences, University of Washington, Seattle, WA 98195, United States; Fernandez, B.A., Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; Folstein, S.E., Disciplines of Genetics and Medicine, Memorial University of Newfoundland, St Johns, NL A1B 3V6, Canada; Fombonne, E., John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33101, United States; Freitag, C.M., Division of Psychiatry, McGill University, Montreal, QC H3A 1A1, Canada; Gilbert, J., Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, J.W. Goethe University Frankfurt, 60528 Frankfurt, Germany; Gillberg, C., John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33101, United States; Glessner, J.T., Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg S41345, Sweden; Goldberg, J., Center for Applied Genomics, Division of Human Genetics, Childrens Hospital of Philadelphia, Philadelphia, PA 19104, United States; Green, A., Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON L8N 3Z5, Canada; Green, J., School of Medicine, Medical Science University College, Dublin 4, Iran; Guter, S.J., Academic Department of Child Psychiatry, Booth Hall of Childrens Hospital, Blackley, Manchester M9 7AA, United Kingdom; Hakonarson, H., Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, United States; Heron, E.A., Center for Applied Genomics, Division of Human Genetics, Childrens Hospital of Philadelphia, Philadelphia, PA 19104, United States, Department of Pediatrics, Childrens Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States; Hill, M., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Holt, R., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Howe, J.L., Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; Hughes, G., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Hus, V., Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Iran; Igliozzi, R., Autism and Communicative Disorders Centre, University of Michigan, Ann Arbor, MI 48109-2054, United States; Kim, C., Stella Maris Institute for Child and Adolescent Neuropsychiatry, 56128 Calambrone (Pisa), Italy; Klauck, S.M., Center for Applied Genomics, Division of Human Genetics, Childrens Hospital of Philadelphia, Philadelphia, PA 19104, United States; Kolevzon, A., Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Korvatska, O., Seaver Autism Center for Research and Treatment, Department of Psychiatry, Mount Sinai School of Medicine, NY 10029, United States; Kustanovich, V., Department of Medicine, University of Washington, Seattle, WA 98195, United States; Lajonchere, C.M., Autism Genetic Resource Exchange, Autism Speaks, Los Angeles, CA 90036-4234, United States; Lamb, J.A., Autism Genetic Resource Exchange, Autism Speaks, Los Angeles, CA 90036-4234, United States; Laskawiec, M., Centre for Integrated Genomic Medical Research, University of Manchester, Manchester M13 9PT, United Kingdom; Leboyer, M., Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford OX3 7JX, United Kingdom; Le Couteur, A., Department of Psychiatry, Groupe Hospitalier Henri Mondor-Albert Chenevier, University Paris 12, Créteil 94000, France; Leventhal, B.L., Child and Adolescent Mental Health, University of Newcastle, Sir James Spence Institute, Newcastle upon Tyne NE1 4LP, United Kingdom, Insitutes of Neuroscience and Health and Society, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom; Lionel, A.C., Nathan Kline Institute for Psychiatric Research (NKI), 140 Old Orangeburg Road, Orangeburg, NY 10962, United States, Department of Child and Adolescent Psychiatry, New York University and NYU Child Study Center, 550 First Avenue, New York, NY 10016, United States; Liu, X.-Q., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Lord, C., Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; Lotspeich, L., Autism and Communicative Disorders Centre, University of Michigan, Ann Arbor, MI 48109-2054, United States; Lund, S.C., Department of Psychiatry, Division of Child and Adolescent Psychiatry and Child Development, Stanford University School of Medicine, Stanford, CA 94304, United States; Maestrini, E., Department of Molecular Physiology and Biophysics, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN 37232, United States; 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Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable ( ∼90%)3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (&lt;1%frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P=0.012), especially so for loci previously implicated in either ASDand/or intellectual disability (1.69 fold, P=3.4×310-4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways. © 2010 Macmillan Publishers Limited. All rights reserved.",,"guanosine triphosphatase; Ras protein; abnormality; cognition; enzyme activity; genomics; genotype; heritability; mental health; motility; nervous system disorder; article; autism; cell motility; cell proliferation; cognitive development; controlled study; copy number variation; gene locus; genotype; human; intellectual impairment; interpersonal communication; major clinical study; priority journal; social interaction; Case-Control Studies; Cell Movement; Child; Child Development Disorders, Pervasive; Cytoprotection; DNA Copy Number Variations; Europe; Gene Dosage; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Signal Transduction; Social Behavior",,"guanosine triphosphatase, 9059-32-9",,,,"Veenstra-Vanderweele, J., Christian, S.L., Cook Jr., E.H., Autism as a paradigmatic complex genetic disorder (2004) Annu. Rev. Genomics Hum. 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W.; Centre for Applied Genomics and Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada; email: stephen.scherer@sickkids.ca",,,,,,,,00280836,,NATUA,10.1038/nature09146,20531469,"English","Nature",Article,Scopus
"Burns A.R., Wallace I.M., Wildenhain J., Tyers M., Giaever G., Bader G.D., Nislow C., Cutler S.R., Roy P.J.","A predictive model for drug bioaccumulation and bioactivity in Caenorhabditis elegans",2010,"Nature Chemical Biology",6,7,,549,557,,35,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77953805895&partnerID=40&md5=4f794763c9e8ecbc04e991aa8b935ee2","Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom; Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Center for Plant Cell Biology, Department of Botany and Plant Sciences, University of California, Riverside, CA, United States","Burns, A.R., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Wallace, I.M., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Wildenhain, J., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom; Tyers, M., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom; Giaever, G., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada; Bader, G.D., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Nislow, C., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Cutler, S.R., Center for Plant Cell Biology, Department of Botany and Plant Sciences, University of California, Riverside, CA, United States; Roy, P.J., Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada","The resistance of Caenorhabditis elegans to pharmacological perturbation limits its use as a screening tool for novel small bioactive molecules. One strategy to improve the hit rate of small-molecule screens is to preselect molecules that have an increased likelihood of reaching their target in the worm. To learn which structures evade the worm's defenses, we performed the first survey of the accumulation and metabolism of over 1,000 commercially available drug-like small molecules in the worm. We discovered that fewer than 10% of these molecules accumulate to concentrations greater than 50% of that present in the worm's environment. Using our dataset, we developed a structure-based accumulation model that identifies compounds with an increased likelihood of bioavailability and bioactivity, and we describe structural features that facilitate small-molecule accumulation in the worm. Preselecting molecules that are more likely to reach a target by first applying our model to the tens of millions of commercially available compounds will undoubtedly increase the success of future small-molecule screens with C. elegans. © 2010 Nature America, Inc.",,"xenobiotic agent; article; bioaccumulation; Caenorhabditis elegans; chemical analysis; chemical structure; data analysis; mathematical model; nonhuman; prediction; priority journal; xenobiotic metabolism; Animals; Caenorhabditis elegans; Chromatography, High Pressure Liquid; Drug Evaluation, Preclinical; Models, Biological; Molecular Structure; Pharmaceutical Preparations; Structure-Activity Relationship; Caenorhabditis elegans",,"Pharmaceutical Preparations",,,,"Burns, A.R., High-throughput screening of small molecules for bioactivity and target identification in Caenorhabditis elegans (2006) Nat. 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"Warde-Farley D., Donaldson S.L., Comes O., Zuberi K., Badrawi R., Chao P., Franz M., Grouios C., Kazi F., Lopes C.T., Maitland A., Mostafavi S., Montojo J., Shao Q., Wright G., Bader G.D., Morris Q.","The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function",2010,"Nucleic Acids Research",38,SUPPL. 2, gkq537,W214,W220,,113,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77954269901&partnerID=40&md5=3510502728fb9496be38ff909f211d19","Department of Computer Science, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada","Warde-Farley, D., Department of Computer Science, University of Toronto, Toronto, ON, Canada; Donaldson, S.L., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Comes, O., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Zuberi, K., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Badrawi, R., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Chao, P., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Franz, M., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Grouios, C., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Kazi, F., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Lopes, C.T., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Maitland, A., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Mostafavi, S., Department of Computer Science, University of Toronto, Toronto, ON, Canada; Montojo, J., Department of Computer Science, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Shao, Q., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Wright, G., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Bader, G.D., Department of Computer Science, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Morris, Q., Department of Computer Science, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada","GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist. © The Author(s) 2010. Published by Oxford University Press.",,"animal genetics; application service provider; Arabidopsis; article; brain computer interface; Caenorhabditis elegans; computer network; computer prediction; content analysis; controlled study; data mining; data synthesis; Drosophila melanogaster; functional genomics; functional proteomics; gene function; genetic algorithm; genetic database; human computer interaction; human genetics; intermethod comparison; molecular biology; performance measurement system; priority journal; research priority; Saccharomyces cerevisiae; search engine; species difference; web browser; Algorithms; Animals; Gene Regulatory Networks; Genes; Genomics; Humans; Internet; Mice; Software; Arabidopsis thaliana; Caenorhabditis elegans; Drosophila melanogaster; Homo sapiens; Mus musculus; Saccharomyces cerevisiae",,,,,,"Barrett, T., Troup, D.B., Wilhite, S.E., Ledoux, P., Rudnev, D., Evangelista, C., Kim, I.F., Marshall, K.A., NCBI GEO: archive for high-throughput functional genomic data (2009) Nucleic Acids Res., 37, pp. D885-D890; Breitkreutz, B.J., Stark, C., Reguly, T., Boucher, L., Breitkreutz, A., Livstone, M., Oughtred, R., Wood, V., The BioGRID Interaction Database: 2008 update (2008) Nucleic Acids Res., 36, pp. D637-D640; Brown, K.R., Jurisica, I., Online predicted human interaction database (2005) Bioinformatics, 21, pp. 2076-2082; Keshava Prasad, T.S., Goel, R., Kandasamy, K., Keerthikumar, S., Kumar, S., Mathivanan, S., Telikicherla, D., Venugopal, A., Human Protein Reference Database-2009 update (2009) Nucleic Acids Res., 37, pp. D767-D772; Romero, P., Wagg, J., Green, M.L., Kaiser, D., Krummenacker, M., Karp, P.D., Computational prediction of human metabolic pathways from the complete human genome (2005) Genome Biol., 6, pp. R2; Aranda, B., Achuthan, P., Alam-Faruque, Y., Armean, I., Bridge, A., Derow, C., Feuermann, M., Khadake, J., The IntAct molecular interaction database in 2010 (2010) Nucleic Acids Res., 38, pp. D525-D531; Ceol, A., Chatr Arayamontri, A., Licata, L., Peluso, D., Briganti, L., Perfetto, L., Castagnoli, L., Cesareni, G., MINT, the molecular interaction database: 2009 update (2010) Nucleic Acids Res., 38, pp. D532-D539; Schaefer, C.F., Anthony, K., Krupa, S., Buchoff, J., Day, M., Hannay, T., Buetow, K.H., PID: the Pathway Interaction Database (2009) Nucleic Acids Res., 37, pp. D674-D679; Vastrik, I., D'Eustachio, P., Schmidt, E., Gopinath, G., Croft, D., de Bono, B., Gillespie, M., Matthews, L., Reactome: a knowledge base of biologic pathways and processes (2007) Genome Biol., 8, pp. R39; Mostafavi, S., Ray, D., Warde-Farley, D., Grouios, C., Morris, Q.D., GeneMANIA: a real-time multiple association network integration algorithm for predicitng gene function (2008) Genome Biol., 9, pp. S4; Mostafavi, S., Morris, Q., Fast integration of heterogeneous data sources for predicting gene function with limited annotation (2010) Bioinformatics, , [27 May 2010, Epub ahead of print]; Zhou, D., Bousquet, O., Lal, T., Weston, J., Scholkopf, B., Learning with local and global consistency (2003) Advances in Neural Information Processing Systems 16, pp. 321-328. , Thrun,S., Saul,K. and Scholkopf,B. 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"Hudson T.J., Anderson W., Aretz A., Barker A.D., Bell C., Bernabe R.R., Bhan M.K., Calvo F., Eerola I., Gerhard D.S., Guttmacher A., Guyer M., Hemsley F.M., Jennings J.L., Kerr D., Klatt P., Kolar P., Kusuda J., Lane D.P., Laplace F., Lu Y., Nettekoven G., Ozenberger B., Peterson J., Rao T.S., Remacle J., Schafer A.J., Shibata T., Stratton M.R., Vockley J.G., Watanabe K., Yang H., Yuen M.M.F., Knoppers B.M., Bobrow M., Cambon-Thomsen A., Dressler L.G., Dyke S.O.M., Joly Y., Kato K., Kennedy K.L., Nicolas P., Parker M.J., Rial-Sebbag E., Romeo-Casabona C.M., Shaw K.M., Wallace S., Wiesner G.L., Zeps N., Lichter P., Biankin A.V., Chabannon C., Chin L., Clement B., Alava E.D., Degos F., Ferguson M.L., Geary P., Hayes D.N., Johns A.L., Kasprzyk A., Nakagawa H., Penny R., Piris M.A., Sarin R., Scarpa A., De Vijver M.V., Futreal P.A., Aburatani H., Bayes M., Bowtell D.D.L., Campbel P.J., Estivill X., Grimmond S.M., Gut I., Hirst M., Lopez-Otyn C., Majumder P., Marra M., McPherson J.D., Ning Z., Puente X.S., Ruan Y., Stunnenberg H.G., Swerdlow H., Velculescu V.E., Wilson R.K., Xue H.H., Yang L., Spellman P.T., Bader G.D., Boutros P.C., Flicek P., Getz G., Guigo R., Guo G., Haussler D., Heath S., Hubbard T.J., Jiang T., Jones S.M., Li Q., Lopez-Bigas N., Luo R., Muthuswamy L., Ouellette B.F.F., Pearson J.V., Quesada V., Raphael B.J., Sander C., Speed T.P., Stein L.D., Stuart J.M., Teague J.W., Totoki Y., Tsunoda T., Valencia A., Wheeler D.A., Wu H., Zhao S., Zhou G., Lathrop M., Thomas G., Yoshida T., Axton M., Gunter C., Miller L.J., Zhang J., Haider S.A., Wang J., Yung C.K., Cross A., Liang Y., Gnaneshan S., Guberman J., Hsu J., Chalmers D.R.C., Hasel K.W., Kaan T.S.H., Lowrance W.W., Masui T., Rodriguez L.L., Vergely C., Bowtel D.D.L., Cloonan N., DeFazio A., Eshleman J.R., Etemadmoghadam D., Gardiner B.A., Kench J.G., Sutherland R.L., Tempero M.A., Waddell N.J., Wilson P.J., Gallinger S., Tsao M.-S., Shaw P.A., Petersen G.M., Mukhopadhyay D., DePinho R.A., Thayer S., Shazand K., Beck T., Sam M., Timms L., Ballin V., Ji J., Zhang X., Chen F., Hu X., Yang Q., Tian G., Zhang L., Xing X., Li X., Zhu Z., Yu Y., Yu J., Tost J., Brennan P., Holcatova I., Zaridze D., Brazma A., Egevad L., Prokhortchouk E., Banks R.E., Uhlen M., Viksna J., Ponten F., Skryabin K., Futrea P.A., Birney E., Borg A., Borresen-Dale A.-L., Caldas C., Foekens J.A., Martin S., Reis-Filho J.S., Richardson A.L., Sotiriou C., Veer L.V., Birnbaum D., Blanche H., Boucher P., Boyault S., Masson-Jacquemier J.D., Pauporte I., Pivot X., Vincent-Salomon A., Tabone E., Theillet C., Treilleux I., Bioulac-Sage P., Decaens T., OiseDegos F., Franco D., Gut M., Samuel D., Zucman-Rossi J., Eils R., Brors B., Korbe J.O., Korshunov A., Landgraf P., Lehrach H., Pfister S., Radlwimmer B., Reifenberger G., Taylor M.D., Kalle C.V., Majumder P.P., Rao T.S., Pederzoli P., Lawlor R.T., Delledonne M., Bardelli A., Gress T., Klimstra D., Zamboni G., Nakamura Y., Miyano S., Fujimoto A., Campo E., Sanjose S.D., Montserrat E., Gonzalez-Dyaz M., Jares P., Himmelbaue H., Bea S., Aparicio S., Easton D.F., Collins F.S., Compton C.C., Lander E.S., Burke W., Green A.R., Hamilton S.R., Kallioniemi O.P., Ley T.J., Liu E.T., Wainwright B.J.","International network of cancer genome projects",2010,"Nature",464,7291,,993,998,,301,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77951115122&partnerID=40&md5=b1e5de1255754c16fefb0059242b2fc8","Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada; National Health and Medical Research Council, Canberra, ACT 2601, Australia; German Aerospace Center (DLR), 53175 Bonn, Germany; National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Genome Canada, Ottawa, ON K2P 1P1, Canada; Secretariat of State for Research, Ministry of Science and Innovation, 28027 Madrid, Spain; Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, Delhi 110003, India; Institut National du Cancer, 92513 Boulogne-Billancourt, France; Genomics and Systems Biology Unit, Health Research Directorate, European Commission, B-1049 Brussels, Belgium; Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health, Bethesda, MD 20892, United States; National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Cancer Research UK, London WC2A 3PX, United Kingdom; Sidra Medical and Research Center, Qatar Foundation, Doha, Qatar; Department of Clinical Pharmacology, University of Oxford, Oxford OX2 6HE, United Kingdom; National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan; Division of Molecular Life Sciences, Federal Ministry of Education and Research, 11055 Berlin, Germany; Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; German Cancer Aid, 53113 Bonn, Germany; Wellcome Trust, London NW1 2BE, United Kingdom; National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Yokohama Institute, RIKEN, Yokohama, Kanagawa 230-0045, Japan; BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Hong Kong University of Science and Technology, Hong Kong, Hong Kong; Centre of Genomics and Policy, McGill University, Génome Québec Innovation Centre, Montreal, QC H3A 1A4, Canada; Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom; U558, INSERM, 31073 Toulouse, France; University of North Carolina School of Pharmacy, Division of Pharmaceutical Outcomes and Policy, Institute for Pharmacogenomics and Individualized Therapy, Chapel Hill, NC 27599, United States; Institute for Research in Humanities, Graduate School of Biostudies, Kyoto University, Kyoto, Kyoto 606-8501, Japan; University of Deusto, Bilbao, 48007 Bizkaia, Spain; Ethox Centre, University of Oxford, Oxford OX3 7LF, United Kingdom; Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, United States; Center for Human Genetics, University Hospitals Case Medical Center, Cleveland, OH 44106, United States; St John of God Pathology, Subiaco, WA 6008, Australia; Schools of Surgery and Pathology, Laboratory Medicine, University of Western Australia, Nedlands, WA 6009, Australia; German Cancer Research Center, 69120 Heidelberg, Germany; Garvan Institute of Medical Research, University of New South Wales, Darlinghurst, Sydney, NSW 2010, Australia; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, NSW 2200, Australia; Institut Paoli-Calmettes, 13273 Marseille, France; Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, United States; Department of Dermatology, Harvard Medical School, Boston, MA 02115, United States; U991, INSERM, 35043 Rennes, France; Department of Hematology, Centro de Investigación Del Cáncer, Hospital Universitario, 37007 Salamanca, Spain; Hôpital Beaujon, 92110 Clichy, France; MLF Consulting, Arlington, MA 02474, United States; Canadian Tumour Repository Network, Winnipeg, MB R3M 0V5, Canada; Department of Internal Medicine, Division of Medical Oncology, University of North Carolina, Chapel Hill, NC 27599, United States; Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan; International Genomics Consortium, Phoenix, AZ 85004, United States; Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India; Department of Pathology, University of Verona, 37134 Verona, Italy; Center for Applied Research on Cancer (ARC-NET), Verona University Hospital, 37134 Verona, Italy; Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands; Academic Medical Center, 1015 AZ Amsterdam, Netherlands; Research Center for Advanced Science and Technology, University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan; Center for Genomic Regulation, Pompeu Fabra University, 08003 Barcelona, Spain; Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, 08003 Catalonia, Spain; Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Haematology, University of Cambridge, Cambridge CB2 2XY, United Kingdom; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; CEA/DSV/IG-Centre National de Genotypage, 91057 Evry, France; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Departamento de Bioquý́mica y Biologý́a Molecular, Instituto Universitario de Oncologý ́a, Universidad de Oviedo, 33006 Oviedo, Spain; National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India; Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, Netherlands; Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, United States; Genome Center, Washington University School of Medicine, St. Louis, MO 63108, United States; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, United States; Applied Genomics Center, Fok Ying Tung Graduate School, HKUST, Hong Kong, Hong Kong; Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, Hong Kong; Cancer Institute, Zhejiang University, 310009 Hangzhou, China; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94510, United States; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom; Broad Institute of Harvard, MIT, Cambridge, MA 02142, United States; Spanish National Bioinformatics Institute (INB), Center for Genomic Regulation, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Howard Hughes Medical Institute, Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, United States; Research Unit on Biomedical Informatics, Department of Experimental and Health Science, Pompeu Fabra University, 08003 Barcelona, Spain; Department of Computer Science, Center for Computational Molecular Biology, Brown University, Providence, RI 02912, United States; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Statistics, University of California Berkeley, Berkeley, CA 94720, United States; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, United States; Spanish National Bioinformatics Institute (INB), Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France; Université Claude Bernard Lyon 1, 69622 Villeurbanne, France; Fondation Synergie Lyon Cancer, 69008 Lyon, France; Nature Genetics, New York, NY 10013-1917, United States; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, United States; Nature and the Nature Research Journals, New York, NY 10013, United States; Computer Laboratory, University of Cambridge, Cambridge CB3 0FD, United Kingdom; Faculty of Law, University of Tasmania, Hobart, TAS 7001, Australia; Faculty of Law, National University of Singapore, Singapore 259776, Singapore; Consultant in Health Research Ethics and Policy, 34280 La Grande Motte, France; ISIS 39 Rue Camille Desmoulins, Institut Gustav Roussy, Pediatric Sce, 94805 Villejuif, France; Department of Gynaecological Oncology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; Westmead Institute for Cancer Research, University of Sydney, Westmead Millennium Institute, Westmead, Sydney, NSW 2145, Australia; Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, United States; Department of Anatomical Pathology, Royal Prince Alfred Hospital, University of Sydney, Camperdown, Sydney, NSW 2050, Australia; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States; Department of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4, Canada; Samuel Lunenfeld Research Institute, Toronto, ON M5S 1A1, Canada; Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada; Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada; Department of Health Science Research, Mayo Clinic, Rochester, MI 55905, United States; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MI 55905, United States; Department of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, United States; Department of Surgery, Harvard Medical School, Boston, MA 02115, United States; Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong, Hong Kong; International Agency for Research on Cancer, 69372 Lyon, France; Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, 121 08 Prague, Czech Republic; Department of Epidemiology and Prevention, N. N. Blokhin Russian Cancer Research Centre, Moscow 115478, Russian Federation; Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Bioengineering Center, Russian Academy of Sciences, Moscow 117312, Russian Federation; Cancer Research UK Centre, Leeds Institute for Molecular Medicine, St James's University Hospital, Leeds LS9 7TF, United Kingdom; Science for Life Laboratory, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden; Institute of Mathematics and Computer Science, University of Latvia, Riga LV-1459, Latvia; Uppsala University, SE-751 05 Uppsala, Sweden; Kurchatov Scientific Center, Moscow 123182, Russian Federation; Department of Oncology, Lund University, SE-221 85 Lund, Sweden; Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway; Faculty of Medicine, University of Oslo, 0316 Oslo, Norway; Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, United Kingdom; Department of Medical Oncology, Erasmus MC Rotterdam, Josephine Nefkens Institute, 3015 CE Rotterdam, Netherlands; Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, United Kingdom; Dana-Farber Cancer Institute, Boston, MA 02115, United States; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, United States; Jules Bordet Institute, B-1000 Brussels, Belgium; Centre Léon Bérard, 69373 Lyon, France; Hôpital Jean Minjoz, 25030 Besançon, France; Institut Curie, 75231 Paris, France; Centre Val d'Aurelle Paul-Lamarque, 34298 Montpellier, France; Hôpital Pellegrin, 33076 Bordeaux, France; Hôpital Henri Mondor, 94010 Créteil, France; U955, INSERM, 94000 Créteil, France; Hôpital Antoine Béclère, 92141 Clamart, France; Centre Hepato-Bilaire, AP-HP Hôpital Paul-Brousse, 94800 Villejuif, France; U785, INSERM, 94800 Villejuif, France; U674, INSERM, 75010 Paris, France; BioQuant, Heidelberg University, 69120 Heidelberg, Germany; Genome Biology Unit, European Molecular Biology Laboratory, 69126 Heidelberg, Germany; Department of Neuropathology, Heidelberg University Hospital, 69120 Heidelberg, Germany; Clinic for Pediatric Oncology, Hematology and Immunology, Heinrich-Heine University Hospital, 40225 Düsseldorf, Germany; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany; Institute of Neuropathology, Heinrich-Heine University, 40001 Düsseldorf, Germany; Division of Neurosurgery, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; National Center for Tumor Diseases, 69120 Heidelberg, Germany; Division of Translational Oncology, German Cancer Research Center, 69120 Heidelberg, Germany; Department of Surgery, University Hospital Trust of Verona, 37134 Verona, Italy; Functional Genomics Center, Department of Biotechnology, University of Verona, 37134 Verona, Italy; Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino, 10060 Torino, Italy; FIRC Institute of Molecular Oncology, 20139 Milan, Italy; Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, 35043 Marburg, Germany; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States; Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Hospital Clý́nic, University of Barcelona, 08036 Barcelona, Spain; Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Català d'Oncologia-IDIBELL, 08907 Hospitalet de Llobregat, Spain; BC Cancer Research Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Departments of Public Health and Primary Care and Oncology, University of Cambridge, Cambridge CB1 8RN, United Kingdom; US National Institutes of Health, Bethesda, MD 20892, United States; Department of Bioethics and Humanities, University of Washington, Seattle, WA 98195, United States; Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge CB2 2XY, United Kingdom; Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, United States; Institute for Molecular Medicine Finland, University of Helsinki, FIN-00290 Helsinki, Finland; Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia","Hudson, T.J., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada, Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada; Anderson, W., National Health and Medical Research Council, Canberra, ACT 2601, Australia; Aretz, A., German Aerospace Center (DLR), 53175 Bonn, Germany; Barker, A.D., National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Bell, C., Genome Canada, Ottawa, ON K2P 1P1, Canada; Bernabé, R.R., Secretariat of State for Research, Ministry of Science and Innovation, 28027 Madrid, Spain; Bhan, M.K., Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, Delhi 110003, India; Calvo, F., Institut National du Cancer, 92513 Boulogne-Billancourt, France; Eerola, I., Genomics and Systems Biology Unit, Health Research Directorate, European Commission, B-1049 Brussels, Belgium; Gerhard, D.S., National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Guttmacher, A., Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health, Bethesda, MD 20892, United States; Guyer, M., National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Hemsley, F.M., Cancer Research UK, London WC2A 3PX, United Kingdom; Jennings, J.L., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Kerr, D., Sidra Medical and Research Center, Qatar Foundation, Doha, Qatar, Department of Clinical Pharmacology, University of Oxford, Oxford OX2 6HE, United Kingdom; Klatt, P., Secretariat of State for Research, Ministry of Science and Innovation, 28027 Madrid, Spain; Kolar, P., Genomics and Systems Biology Unit, Health Research Directorate, European Commission, B-1049 Brussels, Belgium; Kusuda, J., National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan; Lane, D.P., Cancer Research UK, London WC2A 3PX, United Kingdom; Laplace, F., Division of Molecular Life Sciences, Federal Ministry of Education and Research, 11055 Berlin, Germany; Lu, Y., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; Nettekoven, G., German Cancer Aid, 53113 Bonn, Germany; Ozenberger, B., National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Peterson, J., National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Rao, T.S., Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, Delhi 110003, India; Remacle, J., Genomics and Systems Biology Unit, Health Research Directorate, European Commission, B-1049 Brussels, Belgium; Schafer, A.J., Wellcome Trust, London NW1 2BE, United Kingdom; Shibata, T., National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan; Stratton, M.R., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Vockley, J.G., National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Watanabe, K., Yokohama Institute, RIKEN, Yokohama, Kanagawa 230-0045, Japan; Yang, H., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Yuen, M.M.F., Hong Kong University of Science and Technology, Hong Kong, Hong Kong; Knoppers, B.M., Centre of Genomics and Policy, McGill University, Génome Québec Innovation Centre, Montreal, QC H3A 1A4, Canada; Bobrow, M., Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom; Cambon-Thomsen, A., U558, INSERM, 31073 Toulouse, France; Dressler, L.G., University of North Carolina School of Pharmacy, Division of Pharmaceutical Outcomes and Policy, Institute for Pharmacogenomics and Individualized Therapy, Chapel Hill, NC 27599, United States; Dyke, S.O.M., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Joly, Y., Centre of Genomics and Policy, McGill University, Génome Québec Innovation Centre, Montreal, QC H3A 1A4, Canada; Kato, K., Institute for Research in Humanities, Graduate School of Biostudies, Kyoto University, Kyoto, Kyoto 606-8501, Japan; Kennedy, K.L., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Nicolás, P., University of Deusto, Bilbao, 48007 Bizkaia, Spain; Parker, M.J., Ethox Centre, University of Oxford, Oxford OX3 7LF, United Kingdom; Rial-Sebbag, E., U558, INSERM, 31073 Toulouse, France; Romeo-Casabona, C.M., University of Deusto, Bilbao, 48007 Bizkaia, Spain; Shaw, K.M., National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Wallace, S., Centre of Genomics and Policy, McGill University, Génome Québec Innovation Centre, Montreal, QC H3A 1A4, Canada; Wiesner, G.L., Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, United States, Center for Human Genetics, University Hospitals Case Medical Center, Cleveland, OH 44106, United States; Zeps, N., St John of God Pathology, Subiaco, WA 6008, Australia, Schools of Surgery and Pathology, Laboratory Medicine, University of Western Australia, Nedlands, WA 6009, Australia; Lichter, P., German Cancer Research Center, 69120 Heidelberg, Germany; Biankin, A.V., Garvan Institute of Medical Research, University of New South Wales, Darlinghurst, Sydney, NSW 2010, Australia, Department of Surgery, Bankstown Hospital, Bankstown, Sydney, NSW 2200, Australia; Chabannon, C., Institut National du Cancer, 92513 Boulogne-Billancourt, France, Institut Paoli-Calmettes, 13273 Marseille, France; Chin, L., Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, United States, Department of Dermatology, Harvard Medical School, Boston, MA 02115, United States; Clément, B., U991, INSERM, 35043 Rennes, France; Alava, E.D., Department of Hematology, Centro de Investigación Del Cáncer, Hospital Universitario, 37007 Salamanca, Spain; Degos, F., Hôpital Beaujon, 92110 Clichy, France; Ferguson, M.L., MLF Consulting, Arlington, MA 02474, United States; Geary, P., Canadian Tumour Repository Network, Winnipeg, MB R3M 0V5, Canada; Hayes, D.N., Department of Internal Medicine, Division of Medical Oncology, University of North Carolina, Chapel Hill, NC 27599, United States; Johns, A.L., Garvan Institute of Medical Research, University of New South Wales, Darlinghurst, Sydney, NSW 2010, Australia; Kasprzyk, A., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Nakagawa, H., Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan; Penny, R., International Genomics Consortium, Phoenix, AZ 85004, United States; Piris, M.A., Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Sarin, R., Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India; Scarpa, A., Department of Pathology, University of Verona, 37134 Verona, Italy, Center for Applied Research on Cancer (ARC-NET), Verona University Hospital, 37134 Verona, Italy; De Vijver, M.V., Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands, Academic Medical Center, 1015 AZ Amsterdam, Netherlands; Futreal, P.A., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Aburatani, H., Research Center for Advanced Science and Technology, University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan; Bayés, M., Center for Genomic Regulation, Pompeu Fabra University, 08003 Barcelona, Spain, Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, 08003 Catalonia, Spain; Bowtell, D.D.L., Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia, Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia; Campbel, P.J., Department of Haematology, University of Cambridge, Cambridge CB2 2XY, United Kingdom, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Estivill, X., Center for Genomic Regulation, Pompeu Fabra University, 08003 Barcelona, Spain, Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, 08003 Catalonia, Spain; Grimmond, S.M., Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; Gut, I., CEA/DSV/IG-Centre National de Genotypage, 91057 Evry, France; Hirst, M., Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; López-Otý́n, C., Departamento de Bioquý́mica y Biologý́a Molecular, Instituto Universitario de Oncologý ́a, Universidad de Oviedo, 33006 Oviedo, Spain; Majumder, P., National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India; Marra, M., Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; McPherson, J.D., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada, Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada; Ning, Z., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Puente, X.S., Departamento de Bioquý́mica y Biologý́a Molecular, Instituto Universitario de Oncologý ́a, Universidad de Oviedo, 33006 Oviedo, Spain; Ruan, Y., Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Stunnenberg, H.G., Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, Netherlands; Swerdlow, H., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Velculescu, V.E., Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, United States; Wilson, R.K., Genome Center, Washington University School of Medicine, St. Louis, MO 63108, United States, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, United States; Xue, H.H., Applied Genomics Center, Fok Ying Tung Graduate School, HKUST, Hong Kong, Hong Kong, Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, Hong Kong; Yang, L., Cancer Institute, Zhejiang University, 310009 Hangzhou, China; Spellman, P.T., Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94510, United States; Bader, G.D., Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Boutros, P.C., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Flicek, P., Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia; Getz, G., Broad Institute of Harvard, MIT, Cambridge, MA 02142, United States; Guigó, R., Spanish National Bioinformatics Institute (INB), Center for Genomic Regulation, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Guo, G., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Haussler, D., Howard Hughes Medical Institute, Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, United States; Heath, S., CEA/DSV/IG-Centre National de Genotypage, 91057 Evry, France; Hubbard, T.J., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Jiang, T., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Jones, S.M., Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Li, Q., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; López-Bigas, N., Research Unit on Biomedical Informatics, Department of Experimental and Health Science, Pompeu Fabra University, 08003 Barcelona, Spain; Luo, R., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Muthuswamy, L., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Ouellette, B.F.F., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Pearson, J.V., Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; Quesada, V., Departamento de Bioquý́mica y Biologý́a Molecular, Instituto Universitario de Oncologý ́a, Universidad de Oviedo, 33006 Oviedo, Spain; Raphael, B.J., Department of Computer Science, Center for Computational Molecular Biology, Brown University, Providence, RI 02912, United States; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States; Speed, T.P., Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia, Department of Statistics, University of California Berkeley, Berkeley, CA 94720, United States; Stein, L.D., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Stuart, J.M., Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, United States; Teague, J.W., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Totoki, Y., National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan; Tsunoda, T., Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan; Valencia, A., Spanish National Bioinformatics Institute (INB), Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Wheeler, D.A., Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; Wu, H., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Zhao, S., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Zhou, G., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Lathrop, M., CEA/DSV/IG-Centre National de Genotypage, 91057 Evry, France, Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France; Thomas, G., Université Claude Bernard Lyon 1, 69622 Villeurbanne, France, Fondation Synergie Lyon Cancer, 69008 Lyon, France; Yoshida, T., National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan; Axton, M., Nature Genetics, New York, NY 10013-1917, United States; Gunter, C., HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, United States; Miller, L.J., Nature and the Nature Research Journals, New York, NY 10013, United States; Zhang, J., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Haider, S.A., Computer Laboratory, University of Cambridge, Cambridge CB3 0FD, United Kingdom; Wang, J., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Yung, C.K., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Cross, A., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Liang, Y., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Gnaneshan, S., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Guberman, J., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Hsu, J., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Chalmers, D.R.C., Faculty of Law, University of Tasmania, Hobart, TAS 7001, Australia; Hasel, K.W., Genome Canada, Ottawa, ON K2P 1P1, Canada; Kaan, T.S.H., Faculty of Law, National University of Singapore, Singapore 259776, Singapore; Lowrance, W.W., Consultant in Health Research Ethics and Policy, 34280 La Grande Motte, France; Masui, T., National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan; Rodriguez, L.L., National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Vergely, C., ISIS 39 Rue Camille Desmoulins, Institut Gustav Roussy, Pediatric Sce, 94805 Villejuif, France; Bowtel, D.D.L., Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia, Department of Surgery, University Hospital Trust of Verona, 37134 Verona, Italy; Cloonan, N., Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; DeFazio, A., Department of Gynaecological Oncology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia, Westmead Institute for Cancer Research, University of Sydney, Westmead Millennium Institute, Westmead, Sydney, NSW 2145, Australia; Eshleman, J.R., Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, United States; Etemadmoghadam, D., Peter MacCallum Cancer Centre, Melbourne, VIC 3002, Australia, Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia; Gardiner, B.A., Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; Kench, J.G., Garvan Institute of Medical Research, University of New South Wales, Darlinghurst, Sydney, NSW 2010, Australia, Department of Anatomical Pathology, Royal Prince Alfred Hospital, University of Sydney, Camperdown, Sydney, NSW 2050, Australia; Sutherland, R.L., Garvan Institute of Medical Research, University of New South Wales, Darlinghurst, Sydney, NSW 2010, Australia; Tempero, M.A., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States; Waddell, N.J., Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; Wilson, P.J., Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4067, Australia; Gallinger, S., Department of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4, Canada, Samuel Lunenfeld Research Institute, Toronto, ON M5S 1A1, Canada; Tsao, M.-S., Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health, Bethesda, MD 20892, United States, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada; Shaw, P.A., Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada; Petersen, G.M., Department of Health Science Research, Mayo Clinic, Rochester, MI 55905, United States; Mukhopadhyay, D., Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MI 55905, United States; DePinho, R.A., Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, United States, Department of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, United States; Thayer, S., Department of Surgery, Harvard Medical School, Boston, MA 02115, United States; Shazand, K., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Beck, T., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Sam, M., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Timms, L., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Ballin, V., Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Ji, J., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; Zhang, X., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Chen, F., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; Hu, X., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Yang, Q., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Tian, G., BGI-Shenzhen, Shenzhen, 518083 Guangdong, China; Zhang, L., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; Xing, X., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; Li, X., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China; Zhu, Z., Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Yu, Y., Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Yu, J., Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong, Hong Kong; Tost, J., CEA/DSV/IG-Centre National de Genotypage, 91057 Evry, France, Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France; Brennan, P., International Agency for Research on Cancer, 69372 Lyon, France; Holcatova, I., Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, 121 08 Prague, Czech Republic; Zaridze, D., Department of Epidemiology and Prevention, N. 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Blokhin Russian Cancer Research Centre, Moscow 115478, Russian Federation; Brazma, A., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom; Egevad, L., Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Prokhortchouk, E., Bioengineering Center, Russian Academy of Sciences, Moscow 117312, Russian Federation; Banks, R.E., Cancer Research UK Centre, Leeds Institute for Molecular Medicine, St James's University Hospital, Leeds LS9 7TF, United Kingdom; Uhlén, M., Science for Life Laboratory, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden; Viksna, J., Institute of Mathematics and Computer Science, University of Latvia, Riga LV-1459, Latvia; Ponten, F., Uppsala University, SE-751 05 Uppsala, Sweden; Skryabin, K., Kurchatov Scientific Center, Moscow 123182, Russian Federation; Futrea, P.A., Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Birney, E., European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, United Kingdom; Borg, A., Department of Oncology, Lund University, SE-221 85 Lund, Sweden; Børresen-Dale, A.-L., Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway; Caldas, C., Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, United Kingdom; Foekens, J.A., Department of Medical Oncology, Erasmus MC Rotterdam, Josephine Nefkens Institute, 3015 CE Rotterdam, Netherlands; Martin, S., Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; Reis-Filho, J.S., Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, United Kingdom; Richardson, A.L., Dana-Farber Cancer Institute, Boston, MA 02115, United States, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, United States; Sotiriou, C., Jules Bordet Institute, B-1000 Brussels, Belgium; Veer, L.V., Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands; Birnbaum, D., Institut Paoli-Calmettes, 13273 Marseille, France; Blanche, H., Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France; Boucher, P., Institut National du Cancer, 92513 Boulogne-Billancourt, France; Boyault, S., Centre Léon Bérard, 69373 Lyon, France; Masson-Jacquemier, J.D., Institut Paoli-Calmettes, 13273 Marseille, France; Pauporté, I., Institut National du Cancer, 92513 Boulogne-Billancourt, France; Pivot, X., Hôpital Jean Minjoz, 25030 Besançon, France; Vincent-Salomon, A., Institut Curie, 75231 Paris, France; Tabone, E., Centre Léon Bérard, 69373 Lyon, France; Theillet, C., Centre Val d'Aurelle Paul-Lamarque, 34298 Montpellier, France; Treilleux, I., Centre Léon Bérard, 69373 Lyon, France; Bioulac-Sage, P., Hôpital Pellegrin, 33076 Bordeaux, France; Decaens, T., Hôpital Henri Mondor, 94010 Créteil, France, U955, INSERM, 94000 Créteil, France; OiseDegos, F., Hôpital Beaujon, 92110 Clichy, France; Franco, D., Hôpital Antoine Béclère, 92141 Clamart, France; Gut, M., Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France; Samuel, D., Centre Hepato-Bilaire, AP-HP Hôpital Paul-Brousse, 94800 Villejuif, France, U785, INSERM, 94800 Villejuif, France; Zucman-Rossi, J., U674, INSERM, 75010 Paris, France; Eils, R., German Cancer Research Center, 69120 Heidelberg, Germany, BioQuant, Heidelberg University, 69120 Heidelberg, Germany; Brors, B., German Cancer Research Center, 69120 Heidelberg, Germany; Korbe, J.O., Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China, Genome Biology Unit, European Molecular Biology Laboratory, 69126 Heidelberg, Germany; Korshunov, A., Department of Neuropathology, Heidelberg University Hospital, 69120 Heidelberg, Germany; Landgraf, P., Clinic for Pediatric Oncology, Hematology and Immunology, Heinrich-Heine University Hospital, 40225 Düsseldorf, Germany; Lehrach, H., Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Pfister, S., German Cancer Research Center, 69120 Heidelberg, Germany, Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany; Radlwimmer, B., German Cancer Research Center, 69120 Heidelberg, Germany; Reifenberger, G., Institute of Neuropathology, Heinrich-Heine University, 40001 Düsseldorf, Germany; Taylor, M.D., Division of Neurosurgery, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Kalle, C.V., National Center for Tumor Diseases, 69120 Heidelberg, Germany, Division of Translational Oncology, German Cancer Research Center, 69120 Heidelberg, Germany; Majumder, P.P., National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada; Rao, T.S., Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, Delhi 110003, India; Pederzoli, P., Department of Surgery, University Hospital Trust of Verona, 37134 Verona, Italy; Lawlor, R.T., Center for Applied Research on Cancer (ARC-NET), Verona University Hospital, 37134 Verona, Italy; Delledonne, M., Functional Genomics Center, Department of Biotechnology, University of Verona, 37134 Verona, Italy; Bardelli, A., Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino, 10060 Torino, Italy, FIRC Institute of Molecular Oncology, 20139 Milan, Italy; Gress, T., Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, 35043 Marburg, Germany; Klimstra, D., Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States; Zamboni, G., Department of Pathology, University of Verona, 37134 Verona, Italy; Nakamura, Y., Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan, Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Miyano, S., Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Fujimoto, A., Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan; 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Compton, C.C., National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, United States; Lander, E.S., Broad Institute of Harvard, MIT, Cambridge, MA 02142, United States; Burke, W., Department of Bioethics and Humanities, University of Washington, Seattle, WA 98195, United States; Green, A.R., Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge CB2 2XY, United Kingdom; Hamilton, S.R., Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, United States; Kallioniemi, O.P., Institute for Molecular Medicine Finland, University of Helsinki, FIN-00290 Helsinki, Finland; Ley, T.J., Genome Center, Washington University School of Medicine, St. Louis, MO 63108, United States, Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States; Liu, E.T., Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore; Wainwright, B.J., Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia","The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies. © 2010 Macmillan Publishers Limited. All rights reserved.",,"methyltransferase; transcriptome; cancer; disease control; disease treatment; genomics; international cooperation; mutation; tumor; amino acid substitution; angiogenesis; cancer genetics; cancer invasion; cancer research; cancer therapy; DNA methylation; epigenetics; gene deletion; gene insertion; gene mutation; gene rearrangement; genomics; human; international cooperation; metastasis; methylation; oncogene; priority journal; prognosis; review; somatic mutation; tumor gene; Databases, Genetic; DNA Methylation; DNA Mutational Analysis; Genes, Neoplasm; Genetics, Medical; Genome, Human; Genomics; Humans; Intellectual Property; International Cooperation; Mutation; Neoplasms",,"methyltransferase, 9033-25-4",,,,"Stratton, M.R., Campbell, P.J., Futreal, P.A., The cancer genome (2009) Nature, 458, pp. 719-724; Hanahan, D., Weinberg, R.A., The hallmarks of cancer (2000) Cell, 100, pp. 57-70; Slamon, D.J., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 (2001) N. 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Prepublication data sharing (2009) Nature, 461, pp. 168-170; Jones, S., Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene (2009) Science, 324, p. 217; Chin, L., Gray, J.W., Translating insights from the cancer genome into clinical practice (2008) Nature, 452, pp. 553-563","Hudson, T. J.; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; email: tom.hudson@oicr.on.ca",,,,,,,,00280836,,NATUA,10.1038/nature08987,20393554,"English","Nature",Review,Scopus
"Isserlin R., Merico D., Alikhani-Koupaei R., Gramolini A., Bader G.D., Emili A.","Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps",2010,"Proteomics",10,6,,1316,1327,,19,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77949701781&partnerID=40&md5=0323cae9b525b85280e36a72f5db8813","Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada","Isserlin, R., Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Merico, D., Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Alikhani-Koupaei, R., Department of Physiology, University of Toronto, Toronto, ON, Canada; Gramolini, A., Department of Physiology, University of Toronto, Toronto, ON, Canada; Bader, G.D., Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Emili, A., Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada","Global protein expression profiling can potentially uncover perturbations associated with common forms of heart disease. We have used shotgun MS/MS to monitor the state of biological systems in cardiac tissue correlating with disease onset, cardiac insufficiency and progression to heart failure in a time-course mouse model of dilated cardiomyopathy. However, interpreting the functional significance of the hundreds of differentially expressed proteins has been challenging. Here, we utilize improved enrichment statistical methods and an extensive collection of functionally related gene sets, gaining a more comprehensive understanding of the progressive alterations associated with functional decline in dilated cardiomyopathy. We visualize the enrichment results as an Enrichment Map, where significant gene sets are grouped based on annotation similarity. This approach vastly simplifies the interpretation of the large number of enriched gene sets found. For pathways of specific interest, such as Apoptosis and the MAPK (mitogen-activated protein kinase) cascade, we performed a more detailed analysis of the underlying signaling network, including experimental validation of expression patterns. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.","Cardiomyopathy; Gene expression; MS; Pathway analysis; Quantitation; Systems biology","biological marker; brain natriuretic peptide; mitogen activated protein kinase; mutant protein; protein kinase; amino acid sequence; apoptosis; article; congestive cardiomyopathy; data base; gene expression profiling; gene function; heart failure; human; mass spectrometry; priority journal; protein expression; proteomics; quantitative analysis; signal transduction; statistical analysis; validation process; Animals; Apoptosis; Cardiomyopathy, Dilated; Caspase 3; Databases, Protein; Gelsolin; Gene Expression Profiling; MAP Kinase Signaling System; Metabolomics; Mice; Propranolol; Proteomics; Systems Biology; Tandem Mass Spectrometry",,"brain natriuretic peptide, 114471-18-0; mitogen activated protein kinase, 142243-02-5; protein kinase, 9026-43-1; Caspase 3, 3.4.22.-; Gelsolin; Propranolol, 525-66-6",,,,"Rosamond, W., Flegal, K., Furie, K., Go, A., Heart Disease and Stroke Statistics 2008 Update. 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"Costanzo M., Baryshnikova A., Bellay J., Kim Y., Spear E.D., Sevier C.S., Ding H., Koh J.L.Y., Toufighi K., Mostafavi S., Prinz J., St. Onge R.P., Vandersluis B., Makhnevych T., Vizeacoumar F.J., Alizadeh S., Bahr S., Brost R.L., Chen Y., Cokol M., Deshpande R., Li Z., Lin Z.-Y., Liang W., Marback M., Paw J., Luis B.-J.S., Shuteriqi E., Tong A.H.Y., Van Dyk N., Wallace I.M., Whitney J.A., Weirauch M.T., Zhong G., Zhu H., Houry W.A., Brudno M., Ragibizadeh S., Papp B., Pal C., Roth F.P., Giaever G., Nislow C., Troyanskaya O.G., Bussey H., Bader G.D., Gingras A.-C., Morris Q.D., Kim P.M., Kaiser C.A., Myers C.L., Andrews B.J., Boone C.","The genetic landscape of a cell",2010,"Science",327,5964,,425,431,,524,"http://www.scopus.com/inward/record.url?eid=2-s2.0-75649111192&partnerID=40&md5=d55f20ddb1d6cf6a39b58c9174009aed","Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, United States; Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada; Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, United States; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, United States; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Pharmacy, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, United States; SandP Robotics, Inc., 1181 Finch Avenue West, North York, ON M3J 2V8, Canada; Institute of Biochemistry, Biological Research Center, H-6701 Szeged, Hungary; Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, United States; Biology Department, McGill University, Montreal, QC H3A 1B1, Canada","Costanzo, M., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Baryshnikova, A., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Bellay, J., Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; Kim, Y., Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; Spear, E.D., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, United States; Sevier, C.S., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, United States; Ding, H., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Koh, J.L.Y., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Toufighi, K., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Mostafavi, S., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada; Prinz, J., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; St. Onge, R.P., Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, United States; Vandersluis, B., Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; Makhnevych, T., Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Vizeacoumar, F.J., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Alizadeh, S., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Bahr, S., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Brost, R.L., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Chen, Y., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Cokol, M., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, United States; Deshpande, R., Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; Li, Z., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Lin, Z.-Y., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Liang, W., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Marback, M., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Paw, J., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Luis, B.-J.S., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Shuteriqi, E., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Tong, A.H.Y., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Van Dyk, N., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Wallace, I.M., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Pharmacy, University of Toronto, Toronto, ON M5S 3E1, Canada; Whitney, J.A., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada; Weirauch, M.T., Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, United States; Zhong, G., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Zhu, H., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Houry, W.A., Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Brudno, M., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada; Ragibizadeh, S., SandP Robotics, Inc., 1181 Finch Avenue West, North York, ON M3J 2V8, Canada; Papp, B., Institute of Biochemistry, Biological Research Center, H-6701 Szeged, Hungary; Pál, C., Institute of Biochemistry, Biological Research Center, H-6701 Szeged, Hungary; Roth, F.P., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, United States; Giaever, G., Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Pharmacy, University of Toronto, Toronto, ON M5S 3E1, Canada; Nislow, C., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Troyanskaya, O.G., Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, United States; Bussey, H., Biology Department, McGill University, Montreal, QC H3A 1B1, Canada; Bader, G.D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Gingras, A.-C., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Morris, Q.D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Computer Science, University of Toronto, Toronto, ON M5S 2E4, Canada; Kim, P.M., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Kaiser, C.A., Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, United States; Myers, C.L., Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; Andrews, B.J., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Boone, C., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada, Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada","A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for ∼75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.",,"cell organelle; cytology; gene; genome; pleiotropy; yeast; actin filament; article; bioprocess; Caenorhabditis elegans; chemical genetics; DNA modification; endoplasmic reticulum; false negative result; false positive result; fungal gene; gene construct; gene function; gene interaction; gene mapping; gene sequence; genetic conservation; genetic screening; genetic similarity; genome analysis; Golgi complex; morphogenesis; nonhuman; pleiotropy; priority journal; protein protein interaction; quantitative analysis; RNA processing; Saccharomyces cerevisiae; somatic cell genetics; ubiquitination; yeast cell; biology; fungal genome; gene duplication; gene expression regulation; gene regulatory network; genetic fitness; genetics; metabolism; mutation; physiology; protein analysis; Saccharomyces cerevisiae; Saccharomycetales; Saccharomyces cerevisiae protein; Computational Biology; Gene Duplication; Gene Expression Regulation, Fungal; Gene Regulatory Networks; Genes, Fungal; Genetic Fitness; Genome, Fungal; Metabolic Networks and Pathways; Mutation; Protein Interaction Mapping; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins",,"Saccharomyces cerevisiae Proteins",,,,"Dixon, S.J., Costanzo, M., Baryshnikova, A., Andrews, B., Boone, C., (2009) Annu. Rev. Genet., 43, p. 601; Waddington, C.H., (1957) The Strategy of the Gene, , Allen & Unwin, London; Hartwell, L., (2004) Science, 303, p. 774; Tong, A.H., (2001) Science, 294, p. 2364; Tong, A.H., (2004) Science, 303, p. 808; Mani, R., St Onge, R.P., Hartman IV, J.L., Giaever, G., Roth, F.P., (2008) Proc. Natl. Acad. Sci. U.S.A., 105, p. 3461; Science, , Materials and methods are available as supporting material, Online; http://drygin.ccbr.utoronto.ca/~costanzo2009, See supplementary informationSt. Onge, R.P., (2007) Nat. Genet., 39, p. 199; Segrè, D., Deluna, A., Church, G.M., Kishony, R., (2005) Nat. Genet., 37, p. 77; Huber, A., (2009) Genes Dev., 23, p. 1929; Chen, E.J., Kaiser, C.A., (2003) Cell Biol., 161, p. 333; Jonikas, M.C., (2009) Science, 323, p. 1693; Metzger, M.B., Michaelis, S., (2009) Mol. Biol. Cell, 20, p. 1006; Leidel, S., (2009) Nature, 458, p. 228; Rahl, P.B., Chen, C.Z., Collins, R.N., (2005) Mol. Cell, 17, p. 841; Esberg, A., Huang, B., Johansson, M.J., Byström, A.S., (2006) Mol. Cell, 24, p. 139; Naumanen, T., Johansen, L.D., Coffey, E.T., Kallunki, T., (2008) Cell Adh. Migr., 2, p. 236; Johansen, L.D., (2008) J. Cell Sci., 121, p. 854; Levy, S.F., Siegal, M.L., Levchenko, A., (2008) PLoS Biol., 6, pp. e264; Kim, P.M., Lu, L.J., Xia, Y., Gerstein, M.B., (2006) Science, 314, p. 1938; Fraser, H.B., Wall, D.P., Hirsh, A.E., (2003) BMC Evol. Biol., 3, p. 11; Pal, C., Papp, B., Hurst, L.D., (2001) Genetics, 158, p. 927; Kim, P.M., Sboner, A., Xia, Y., Gerstein, M., (2008) Mol. Syst. Biol., 4, p. 179; Lehner, B., Crombie, C., Tischler, J., Fortunato, A., Fraser, A.G., (2006) Nat. Genet, 38, p. 896; Hillenmeyer, M.E., (2008) Science, 320, p. 362; Dunham, M.J., (2002) Proc. Natl. Acad. Sci. U.S.A., 99, p. 16144; Gavin, A.C., (2006) Nature, 440, p. 631; Krogan, N.J., (2006) Nature, 440, p. 637; Yu, H., (2008) Science, 322, p. 104; Tarassov, K., (2008) Science, 320, p. 1465; De Visser, J.A., (2003) Evolution, 57, p. 1959; Meiklejohn, C.D., Hartl, D.L., (2002) Trends Ecol. Evol., 17, p. 468; Parsons, A.B., (2004) Nat Biotechnol., 22, p. 62; Sevier, C.S., (2007) Cell, 129, p. 333; Fong, P.C., (2009) N. Engl. J. Med., 361, p. 123; Lehár, J., Stockwell, B.R., Giaever, G., Nislow, C., (2008) Nat. Chem. Biol., 4, p. 674; We thank S. Dixon, T. Hughes, P. Jorgensen, and M. Tyers for critical comments. Supported by Genome Canada through the Ontario Genomics Institute (2004-OGI-3-01) and the Canadian Institutes of Health Research (GSP-41567) (C.B., B.A.), the University of Minnesota Biomedical Informatics and Computational Biology program (J.B., R.D.), and a seed grant from the Minnesota Supercomputing Institute (J.B., B.V.)","Myers, C. L.; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, United States; email: cmyers@cs.umn.edu",,,,,,,,00368075,,SCIEA,10.1126/science.1180823,20093466,"English","Science",Article,Scopus
"Kandasamy K., Sujatha Mohan S., Raju R., Keerthikumar S., Sameer Kumar G.S., Venugopal A.K., Telikicherla D., Navarro D.J., Mathivanan S., Pecquet C., Gollapudi S.K., Tattikota S.G., Mohan S., Padhukasahasram H., Subbannayya Y., Goel R., Jacob H.K., Zhong J., Sekhar R., Nanjappa V., Balakrishnan L., Subbaiah R., Ramachandra Y.L., Abdul Rahiman B., Keshava Prasad T.S., Lin J.-X., Houtman J.C., Desiderio S., Renauld J.-C., Constantinescu S., Ohara O., Hirano T., Kubo M., Singh S., Khatri P., Draghici S., Bader G.D., Sander C., Leonard W.J., Pandey A.","NetPath: A public resource of curated signal transduction pathways",2010,"Genome Biology",11,1, r3,,,,45,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77349091815&partnerID=40&md5=573bf3bca50b991a58b6995eafa3bd67","Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; McKusick-Nathans Institute of Genetic Medicine, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, United States; The Ludwig Institute for Cancer Research, Brussels Branch, and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Universite Catholique de Louvain, Avenue Hippocrate 74, B-1200-Brussels, Belgium; Department of Biotechnology and Bioinformatics, Kuvempu University, Jnanasahyadri, Shimoga 577451, India; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, United States; Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States; Department of Molecular Biology and Genetics, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan; Department of Human Genome Technology, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan; Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Laboratories of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki, Noda City, Chiba 278-0022, Japan; Signal/Network Team, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Suehiro-cho, Tsurumi, Yokohama, Kanagawa230-0045, Japan; IMGENEX India Pvt. Ltd., Bhubaneswar, Orissa 92121, India; Department of Computer Science, Wayne State University, Detroit, Michigan 48202, United States; Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48202, United States; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St., Toronto, Ontario M5S 3E1, Canada; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York 10021, United States; Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21205, United States; Research Unit for Immunoinformatics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa, Japan","Kandasamy, K., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, McKusick-Nathans Institute of Genetic Medicine, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, United States; Sujatha Mohan, S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Research Unit for Immunoinformatics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa, Japan; Raju, R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, Department of Biotechnology and Bioinformatics, Kuvempu University, Jnanasahyadri, Shimoga 577451, India; Keerthikumar, S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Sameer Kumar, G.S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Venugopal, A.K., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Telikicherla, D., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Navarro, D.J., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Mathivanan, S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Pecquet, C., The Ludwig Institute for Cancer Research, Brussels Branch, and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Universite Catholique de Louvain, Avenue Hippocrate 74, B-1200-Brussels, Belgium; Gollapudi, S.K., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Tattikota, S.G., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Mohan, S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Padhukasahasram, H., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Subbannayya, Y., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Goel, R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Jacob, H.K., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India, McKusick-Nathans Institute of Genetic Medicine, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, United States; Zhong, J., McKusick-Nathans Institute of Genetic Medicine, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, United States; Sekhar, R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Nanjappa, V., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Balakrishnan, L., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Subbaiah, R., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Ramachandra, Y.L., Department of Biotechnology and Bioinformatics, Kuvempu University, Jnanasahyadri, Shimoga 577451, India; Abdul Rahiman, B., Department of Biotechnology and Bioinformatics, Kuvempu University, Jnanasahyadri, Shimoga 577451, India; Keshava Prasad, T.S., Institute of Bioinformatics, International Tech Park, Bangalore 560066, India; Lin, J.-X., Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, United States; Houtman, J.C., Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States; Desiderio, S., Department of Molecular Biology and Genetics, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States; Renauld, J.-C., The Ludwig Institute for Cancer Research, Brussels Branch, and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Universite Catholique de Louvain, Avenue Hippocrate 74, B-1200-Brussels, Belgium; Constantinescu, S., The Ludwig Institute for Cancer Research, Brussels Branch, and the Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, Universite Catholique de Louvain, Avenue Hippocrate 74, B-1200-Brussels, Belgium; Ohara, O., Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa 230-0045, Japan, Department of Human Genome Technology, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan; Hirano, T., Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan, Laboratories of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Kubo, M., Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki, Noda City, Chiba 278-0022, Japan, Signal/Network Team, RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Suehiro-cho, Tsurumi, Yokohama, Kanagawa230-0045, Japan; Singh, S., IMGENEX India Pvt. Ltd., Bhubaneswar, Orissa 92121, India; Khatri, P., Department of Computer Science, Wayne State University, Detroit, Michigan 48202, United States; Draghici, S., Department of Computer Science, Wayne State University, Detroit, Michigan 48202, United States, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48202, United States; Bader, G.D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St., Toronto, Ontario M5S 3E1, Canada, Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York 10021, United States; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York 10021, United States; Leonard, W.J., Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, United States; Pandey, A., McKusick-Nathans Institute of Genetic Medicine, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, United States, Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21205, United States","We have developed NetPath as a resource of curated human signaling pathways. As an initial step, NetPath provides detailed maps of a number of immune signaling pathways, which include ~1,600 reactions annotated from the literature and more than 2,800 instances of transcriptionally-regulated genes - all linked to over 5,500 published articles. We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches. © 2010 Kandasamy et al. , licensee BioMed Central Ltd.",,"interleukin 2; access to information; article; gene mapping; human; information retrieval; intermethod comparison; Internet; medical literature; microarray analysis; NetPath; Northern blotting; protein interaction; protein processing; reference database; reverse transcription polymerase chain reaction; serial analysis of gene expression; signal transduction; systems biology; transcription regulation; animal; apoptosis; biochemistry; biological model; biology; cell motion; computer program; factual database; genetic transcription; immune system; metabolism; methodology; protein analysis; Access to Information; Animals; Apoptosis; Biochemistry; Cell Movement; Computational Biology; Databases, Factual; Humans; Immune System; Interleukin-2; Models, Biological; Models, Genetic; Protein Interaction Mapping; Signal Transduction; Software; Transcription, Genetic",,"interleukin 2, 85898-30-2; Interleukin-2",,,,"Fukuda, K., Takagi, T., Knowledge representation of signal transduction pathways (2001) Bioinformatics, 17, pp. 829-837; Uetz, P., Finley R.L., Jr., From protein networks to biological systems (2005) FEBS Lett, 579, pp. 1821-1827; Ideker, T., A systems approach to discovering signaling and regulatory pathways--or, how to digest large interaction networks into relevant pieces (2004) Adv Exp Med Biol, 547, pp. 21-30; Schaefer, C.F., Pathway databases (2004) Ann N Y Acad Sci, 1020, pp. 77-91; http://www.netpath.org/, NetPathKandasamy, K., Keerthikumar, S., Raju, R., Keshava Prasad, T.S., Ramachandra, Y.L., Mohan, S., Pandey, A., PathBuilder--open source software for annotating and developing pathway resources (2009) Bioinformatics, 25, pp. 2860-2862; http://www.biopax.org/, BioPAX: Biological Pathways ExchangeHermjakob, H., Montecchi-Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., Ceol, A., Moore, S., Jacq, B., The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data (2004) Nat Biotechnol, 22, pp. 177-183; Hucka, M., Finney, A., Sauro, H.M., Bolouri, H., Doyle, J.C., Kitano, H., Arkin, A.P., Mjolsness, E.D., The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models (2003) Bioinformatics, 19, pp. 524-531; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: a software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504; http://cancer.cellmap.org/, The Cancer Cell MapBader, G.D., Cary, M.P., Sander, C., Pathguide: a pathway resource list (2006) Nucleic Acids Res, 34, pp. D504-506; Kanehisa, M., Goto, S., KEGG: kyoto encyclopedia of genes and genomes (2000) Nucleic Acids Res, 28, pp. 27-30; http://www.biocarta.com/, BioCartahttp://stke.sciencemag.org/, Connections MapsJoshi-Tope, G., Gillespie, M., Vastrik, I., D'Eustachio, P., Schmidt, E., de Bono, B., Jassal, B., Stein, L., Reactome: a knowledgebase of biological pathways (2005) Nucleic Acids Res, 33, pp. D428-432; http://pid.nci.nih.gov/, NCI-Nature Pathway Interaction Databasehttp://www.cellsignal.com/, Cell Signaling Technologyhttp://www.inoh.org/, INOH Pathway Databasehttp://www.grt.kyushu-u.ac.jp/spad, Signaling Pathway DatabaseHackl, H., Maurer, M., Mlecnik, B., Hartler, J., Stocker, G., Miranda-Saavedra, D., Trajanoski, Z., GOLD.db: genomics of lipid-associated disorders database (2004) BMC Genomics, 5, p. 93; Demir, E., Babur, O., Dogrusoz, U., Gursoy, A., Nisanci, G., Cetin-Atalay, R., Ozturk, M., PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways (2002) Bioinformatics, 18, pp. 996-1003; Ng, A., Bursteinas, B., Gao, Q., Mollison, E., Zvelebil, M., pSTIING: a 'systems' approach towards integrating signalling pathways, interaction and transcriptional regulatory networks in inflammation and cancer (2006) Nucleic Acids Res, 34, pp. D527-534; Zheng, C.J., Zhou, H., Xie, B., Han, L.Y., Yap, C.W., Chen, Y.Z., TRMP: a database of therapeutically relevant multiple pathways (2004) Bioinformatics, 20, pp. 2236-2241; Pico, A.R., Kelder, T., van Iersel, M.P., Hanspers, K., Conklin, B.R., Evelo, C., WikiPathways: pathway editing for the people (2008) PLoS Biol, 6, pp. e184; Thomas, P.D., Campbell, M.J., Kejariwal, A., Mi, H., Karlak, B., Daverman, R., Diemer, K., Narechania, A., PANTHER: a library of protein families and subfamilies indexed by function (2003) Genome Res, 13, pp. 2129-2141; Nakamura, M., Asao, H., Takeshita, T., Sugamura, K., Interleukin-2 receptor heterotrimer complex and intracellular signaling (1993) Semin Immunol, 5, pp. 309-317; Morgan, D.A., Ruscetti, F.W., Gallo, R., Selective in vitro growth of T lymphocytes from normal human bone marrows (1976) Science, 193, pp. 1007-1008; Mingari, M.C., Gerosa, F., Carra, G., Accolla, R.S., Moretta, A., Zubler, R.H., Waldmann, T.A., Moretta, L., Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells (1984) Nature, 312, pp. 641-643; London, L., Perussia, B., Trinchieri, G., Induction of proliferation in vitro of resting human natural killer cells: IL 2 induces into cell cycle most peripheral blood NK cells, but only a minor subset of low density T cells (1986) J Immunol, 137, pp. 3845-3854; Grimm, E.A., Mazumder, A., Zhang, H.Z., Rosenberg, S.A., Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes (1982) J Exp Med, 155, pp. 1823-1841; Greene, W.C., Leonard, W.J., The human interleukin-2 receptor (1986) Annu Rev Immunol, 4, pp. 69-95; Green, D.R., Droin, N., Pinkoski, M., Activation-induced cell death in T cells (2003) Immunol Rev, 193, pp. 70-81; Malek, T.R., Bayer, A.L., Tolerance, not immunity, crucially depends on IL-2 (2004) Nat Rev Immunol, 4, pp. 665-674; Rosenberg, S.A., Progress in human tumour immunology and immunotherapy (2001) Nature, 411, pp. 380-384; Paredes, R., Lopez Benaldo de Quiros, J.C., Fernandez-Cruz, E., Clotet, B., Lane, H.C., The potential role of interleukin-2 in patients with HIV infection (2002) AIDS Rev, 4, pp. 36-40; Kim, H.P., Imbert, J., Leonard, W.J., Both integrated and differential regulation of components of the IL-2/IL-2 receptor system (2006) Cytokine Growth Factor Rev, 17, pp. 349-366; Leonard, W.J., Type I Cytokines and Interferons and Their Receptors, , Sixth edn. Philadelphia: Lippincott Williams & Wilkins; Noguchi, M., Yi, H., Rosenblatt, H.M., Filipovich, A.H., Adelstein, S., Modi, W.S., McBride, O.W., Leonard, W.J., Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans (1993) Cell, 73, pp. 147-157; Lin, J.X., Leonard, W.J., Signaling from the IL-2 receptor to the nucleus (1997) Cytokine Growth Factor Rev, 8, pp. 313-332; Ellery, J.M., Nicholls, P.J., Alternate signalling pathways from the interleukin-2 receptor (2002) Cytokine Growth Factor Rev, 13, pp. 27-40; Ahmed, N.N., Grimes, H.L., Bellacosa, A., Chan, T.O., Tsichlis, P.N., Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase (1997) Proc Natl Acad Sci U S A, 94, pp. 3627-3632; http://www.hprd.org/, HPRD: Human Protein Reference DatabasePeri, S., Navarro, J.D., Amanchy, R., Kristiansen, T.Z., Jonnalagadda, C.K., Surendranath, V., Niranjan, V., Joy, M., Development of human protein reference database as an initial platform for approaching systems biology in humans (2003) Genome Res, 13, pp. 2363-2371; Mishra, G.R., Suresh, M., Kumaran, K., Kannabiran, N., Suresh, S., Bala, P., Shivakumar, K., Vishnupriya, G., Human protein reference database--2006 update (2006) Nucleic Acids Res, 34, pp. D411-414; Cary, M.P., Bader, G.D., Sander, C., Pathway information for systems biology (2005) FEBS Lett, 579, pp. 1815-1820; http://creativecommons.org/licenses/by/2.5/, Creative Commons license version 2.5Draghici, S., Khatri, P., Tarca, A.L., Amin, K., Done, A., Voichita, C., Georgescu, C., Romero, R., A systems biology approach for pathway level analysis (2007) Genome Res, 17, pp. 1537-1545; Barrett, T., Troup, D.B., Wilhite, S.E., Ledoux, P., Rudnev, D., Evangelista, C., Kim, I.F., Edgar, R., NCBI GEO: mining tens of millions of expression profiles--database and tools update (2007) Nucleic Acids Res, 35, pp. D760-765; Eliezer Silva, J.A., He, Q., Svetkauskaite, D., Coldren, C., Nick, J.A., Poch, K., Park, J.S., Abraham, E., HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury (2007) Intensive Care Medicine, 33, pp. 1829-1839; Wurfel, M.M., Park, W.Y., Radella, F., Ruzinski, J., Sandstrom, A., Strout, J., Bumgarner, R.E., Martin TR: Identification of high and low responders to lipopolysaccharide in normal subjects: an unbiased approach to identify modulators of innate immunity (2005) J Immunol, 175, pp. 2570-2578; Pathway Commons http://www.pathwaycommons.org/van Iersel, M.P., Kelder, T., Pico, A.R., Hanspers, K., Coort, S., Conklin, B.R., Evelo, C., Presenting and exploring biological pathways with PathVisio (2008) BMC Bioinformatics, 9, p. 399; Hoffmann, R., Valencia, A., A gene network for navigating the literature (2004) Nat Genet, 36, p. 664","Pandey, A.; McKusick-Nathans Institute of Genetic Medicine, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205, United States; email: pandey@jhmi.edu",,,,,,,,14747596,,GNBLF,10.1186/gb-2010-11-1-r3,20067622,"English","Genome Biol.",Article,Scopus
"Koh J.L.Y., Ding H., Costanzo M., Baryshnikova A., Toufighi K., Bader G.D., Myers C.L., Andrews B.J., Boone C.","DRYGIN: A database of quantitative genetic interaction networks in yeast",2010,"Nucleic Acids Research",38,SUPPL.1, gkp820,D502,D507,,27,"http://www.scopus.com/inward/record.url?eid=2-s2.0-75549091259&partnerID=40&md5=2002c423086ec89593c870fb0f729ba6","Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Department of Computer Science and Engineering, University of Minnesota, 4-192 EE/CS Building, 200 Union Street SE, Minneapolis, MN 55455, United States","Koh, J.L.Y., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Ding, H., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Costanzo, M., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Baryshnikova, A., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Toufighi, K., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Bader, G.D., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Myers, C.L., Department of Computer Science and Engineering, University of Minnesota, 4-192 EE/CS Building, 200 Union Street SE, Minneapolis, MN 55455, United States; Andrews, B.J., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Boone, C., Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","Genetic interactions are highly informative for deciphering the underlying functional principles that govern how genes control cell processes. Recent developments in Synthetic Genetic Array (SGA) analysis enable the mapping of quantitative genetic interactions on a genome-wide scale. To facilitate access to this resource, which will ultimately represent a complete genetic interaction network for a eukaryotic cell, we developed DRYGIN (Data Repository of Yeast Genetic Interactions)-a web database system that aims at providing a central platform for yeast genetic network analysis and visualization. In addition to providing an interface for searching the SGA genetic interactions, DRYGIN also integrates other data sources, in order to associate the genetic interactions with pathway information, protein complexes, other binary genetic and physical interactions, and Gene Ontology functional annotation. DRYGIN version 1.0 currently holds more than 5.4 million measurements of genetic interacting pairs involving ~4500 genes, and is available at http://drygin.ccbr.utoronto.ca © The Author(s) 2009. Published by Oxford University Press.",,"access to information; article; controlled study; Data Repository of Yeast Genetic Interactions database; eukaryotic cell; gene interaction; gene mapping; genetic database; Internet; nonhuman; priority journal; quantitative analysis; Saccharomyces cerevisiae; biological model; biology; computer program; fungal gene; fungal genome; genetics; information retrieval; methodology; nucleic acid database; protein analysis; protein database; protein tertiary structure; Eukaryota; fungal protein; Computational Biology; Databases, Genetic; Databases, Nucleic Acid; Databases, Protein; Fungal Proteins; Genes, Fungal; Genome, Fungal; Information Storage and Retrieval; Internet; Models, Genetic; Protein Interaction Mapping; Protein Structure, Tertiary; Software",,"Fungal Proteins",,,,"Boone, C., Bussey, H., Andrews, B.J., Exploring genetic interactions and networks with yeast (2007) Nat. Rev., 8, pp. 1641-1649; Tong, A.H.Y., Evangelista, M., Parson, A.B., Xu, H., Bader, G.D., Page, N., Robinson, M., Bussey, H., Systematic genetic analysis with ordered arrays of yeast deletion mutants (2001) Science, 294, pp. 2365-2368; Tong, A.H., Lesage, G., Bader, G.D., Ding, H., Xu, H., Xin, X., Young, J., Chang, M., Global mapping of the yeast genetic interaction network (2004) Science, 303, pp. 808-813; Dixon, S.J., Fedyshyn, Y., Koh, J.L.Y., Prasad, T.S., Chahwan, C., Chua, G., Toufighi, K., Hoe, K., Significant conservation of synthetic lethal genetic interaction networks between distantly-related eukaryotes (2008) Proc. Natl Acad. Sci. USA, 105, pp. 16653-16658; Stark, C., Breitkreutz, B.J., Reguly, T., Boucher, L., Breitkreutz, A., Tyers, M., BIOGRID: a general repository for interaction datasets (2006) Nucleic Acids Res., 34, pp. D535-D539; Hirschman, J.E., Balakrishnan, R., Christie, K.R., Costanzo, M.C., Dwight, S.S., Engel, S.R., Fisk, D.G., Nash, R., Genome Snapshot: a new resource at the Saccharomyces Genome Database (SGD) presenting an overview of the Saccharomyces cerevisiae genome (2006) Nucleic Acids Res., 34, pp. D442-D445; Mewes, H.W., Dietmann, S., Frishman, D., Gregory, R., Mannhaupt, G., Mayer, K., Muensterkötter, M., Stuempflen, V., MIPS: analysis and annotation of genome information in 2007 (2008) Nucleic Acids Res., 36, pp. D196-D201; Fisher, R.A., The correlations between relatives on the supposition of Mendelian inheritence (1918) Trans. R. Soc. Edinb., 52, pp. 399-433; Schuldiner, M., Collins, S., Thompson, N., Denic, V., Bhamidipati, A., Punna, T., Ihmels, J., Greenblatt, J., Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile (2005) Cell, 123, pp. 507-519; Beyer, A., Bandyopadhyay, S., Ideker, T., Integrating physical and genetic maps: from genomes to interaction networks (2007) Nat. Rev. Genet., 8, pp. 699-710; Bandyopadhyay, S., Kelley, R., Krogan, N.J., Ideker, T., Functional maps of protein complexes from quantitative genetic interaction data (2008) PLoS Comput. Biol., 4, pp. e1000065; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: a software environment for integrated models of biomolecular interaction networks (2003) Genome Res., 13, pp. 2498-2504; Segrè, D., DeLuna, A., Church, G.M., Kishony, R., Modular epistasis in yeast metabolism (2005) Nat. Genet., 3, pp. 77-83; Pu, S., Wong, J., Turner, B., Cho, E., Wodak, S.J., Up-to-date catalogues of yeast protein complexes (2009) Nucleic Acids Res., 37, pp. 825-831; Kanehisa, M., Araki, M., Goto, S., Hattori, M., Hirakawa, M., Itoh, M., Katayama, T., Tokimatsu, T., KEGG for linking genomes to life and the environment (2008) Nucleic Acids Res., 36, pp. D480-D484; Matthews, L., Gopinath, G., Gillespie, M., Caudy, M., Croft, D., de Bono, B., Garapati, P., Jassal, B., Reactome knowledgebase of human biological pathways and processes (2009) Nucleic Acids Res., 37, pp. D619-D622; Chang, A.N., MacDermott, J., Samudrala, R., An enhanced Java graph applet interface for visualizing interactomes (2005) Bioinformatics, 21, pp. 1741-1742; Saldanha, A.J., Java Treeview-extensible visualization of microarray data (2004) Bioinformatics, 20, pp. 3246-3248; Hermjakob, H., Montecchi-Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., Ceol, A., Moore, S., von Mering, C., The HUPO PSI's molecular interaction format - a community standard for the representation of protein interaction data (2004) Nat. Biotechnol, 22, pp. 177-183","Koh, J.L.Y.; Banting and Best Department of Medical Research and Department of Molecular Genetics, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; email: judice.koh@utoronto.ca",,,,,,,,03051048,,NARHA,10.1093/nar/gkp820,19880385,"English","Nucleic Acids Res.",Article,Scopus
"Tan C.S.H., Pasculescu A., Lim W.A., Pawson T., Bader G.D., Linding R.","Positive selection of tyrosine loss in metazoan evolution",2009,"Science",325,5948,,1686,1688,,40,"http://www.scopus.com/inward/record.url?eid=2-s2.0-70349518562&partnerID=40&md5=89d3ebfb0408bc684cfbdb39c7496289","Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto MSG 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto MSS 3E1, Canada; Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, United States; Cellular and Molecular Logic Team, Section of Cell and Molecular Biology, Institute of Cancer Research (ICR), London, SW3 6JB, United Kingdom","Tan, C.S.H., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto MSG 1X5, Canada, Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto MSS 3E1, Canada; Pasculescu, A., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto MSG 1X5, Canada; Lim, W.A., Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, United States; Pawson, T., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto MSG 1X5, Canada, Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada; Bader, G.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto MSG 1X5, Canada, Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto MSS 3E1, Canada; Linding, R., Cellular and Molecular Logic Team, Section of Cell and Molecular Biology, Institute of Cancer Research (ICR), London, SW3 6JB, United Kingdom","John Nash showed that within a complex system, individuals are best off if they make the best decision that they can, taking into account the decisions of the other individuals. Here, we investigate whether similar principles influence the evolution of signaling networks in multicellular animals. Specifically, by analyzing a set of metazoan species we observed a striking negative correlation of genomically encoded tyrosine content with biological complexity (as measured by the number of cell types in each organism). We discuss how this observed tyrosine loss correlates with the expansion of tyrosine kinases in the evolution of the metazoan lineage and how it may relate to the optimization of signaling systems in multicellular animals. We propose that this phenomenon illustrates genome-wide adaptive evolution to accommodate beneficial genetic perturbation.",,"mitogen activated protein kinase; mixed lineage kinase; phenylalanine; protein tyrosine kinase; tryptophan; adaptation; amino acid; correlation; cytology; enzyme activity; genome; metazoan; optimization; signaling; species diversity; article; cell communication; cell type; genome; metazoon; molecular evolution; nonhuman; priority journal; protein depletion; protein phosphorylation; protein synthesis; proteomics; signal transduction; sulfation; Adaptation, Physiological; Animals; Evolution; Evolution, Molecular; Fungal Proteins; Glycosylation; Humans; Methylation; Mutation; Phosphorylation; Phosphotyrosine; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Proteins; Selection (Genetics); Signal Transduction; Substrate Specificity; Tyrosine; Metazoa",,"mitogen activated protein kinase, 142243-02-5; phenylalanine, 3617-44-5, 63-91-2; protein tyrosine kinase, 80449-02-1; tryptophan, 6912-86-3, 73-22-3; Fungal Proteins; Phosphotyrosine, 21820-51-9; Protein-Tyrosine Kinases, 2.7.1.112; Proteins; Tyrosine, 55520-40-6",,,,"Szathmáry, E., Jordán, F., Pál, C., (2001) Science, 292, p. 1315; Vogel, C., Chothia, C., (2006) PLOS Comput. Biol., 2, pp. e48; Bonner, J.T., (1998) Integ. Biol, 1, p. 28; Hunter, T., (2009) Curr. Opin. Cell Biol., , http://dx.doi.org/10.1016/j.ceb.2009.01.028; Songyang, Z., Cantley, L.C., (1995) Trends Biochem. Sci., 20, p. 470; Zarrinpar, A., Park, S.-H., Lim, W.A., (2003) Nature, 426, p. 676; Materials and methods are available as supporting material on Science OnlineJørgensen, C., Linding, R., (2008) Brief. Funct. Genomics Proteomics, 7, p. 17; Wright, S., (1931) Genetics, 16, p. 97; Raiford, D.W., (2008) J. Mol. Evol., 67, p. 621; Yaffe, M.B., (2001) Nat. Biotechnol., 19, p. 348; Linding, R., (2007) Cell, 129, p. 1415; Miller, M.L., (2008) Sci. Signal., 1, pp. ra2; Seet, B.T., Dikic, I., Zhou, M.-M., Pawson, T., (2006) Nat. Rev. Mol. Cell Biol., 7, p. 473; King, N., (2008) Nature, 451, p. 783; Pincus, D., Letunic, I., Bork, P., Lim, W.A., (2008) Proc. Natl. Acad. Sci. U.S.A., 105, p. 9680; Manning, G., Young, S.L., Miller, W.T., Zhai, Y., (2008) Proc. Natl. Acad. Sci. U.S.A., 105, p. 9674; J. Nash, thesis, Princeton University, Princeton, NJ (1950)We thank C. Jørgensen, J. Zhang, K. Colwill, T. J. Gibson, J. Jin, and K. Lindorff-Larsen for suggestions and fruitful discussions. This project was in part supported by Genome Canada through the Ontario Genomics Institute and the Canadian Institutes of Health Research (MOP-84324). C.S.H.T. conceived the project. C.S.H.T., W.A.L., G.D.B., T.P., and R.L. designed the experiments. C.S.H.T., R.L., and A.P. performed the experiments. C.S.H.T., G.D.B., W.A.L., T.P., and R.L. wrote the paper. R.L. managed the project","Pawson, T.; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto MSG 1X5, Canada; email: pawson@lunenfeld.ca",,,,,,,,00368075,,SCIEA,10.1126/science.1174301,19589966,"English","Science",Article,Scopus
"Tonikian R., Xin X., Toret C.P., Gfeller D., Landgraf C., Panni S., Paoluzi S., Castagnoli L., Currell B., Seshagiri S., Yu H., Winsor B., Vidal M., Gerstein M.B., Bader G.D., Volkmer R., Cesareni G., Drubin D.G., Kim P.M., Sidhu S.S., Boone C.","Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins",2009,"PLoS Biology",7,10, e1000218,,,,65,"http://www.scopus.com/inward/record.url?eid=2-s2.0-70350404403&partnerID=40&md5=f4f2efecf5e502aa643bb964a3d94e5b","Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States; Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Biology, University of Rome Tor Vergata, Rome, Italy; Department of Cell Biology, University of Calabria, Rende, Italy; Department of Molecular Biology, Genentech., South San Francisco, CA, United States; Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States; CNRS, Université de Strasbourg UMR7156, Génétique Moléculaire, Génomique et Microbiologie, Strasbourg, France; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, United States; Department of Computer Science, Yale University, New Haven, CT, United States; Research Institute Fondazione Santa Lucia, Rome, Italy; Department of Protein Engineering, Genentech., South San Francisco, CA, United States; Department of Biological Sciences, Stanford University, Stanford, CA, United States; Department of Genetics, Harvard Medical School, Boston, MA, United States","Tonikian, R., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Xin, X., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Toret, C.P., Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States, Department of Biological Sciences, Stanford University, Stanford, CA, United States; Gfeller, D., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Landgraf, C., Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Panni, S., Department of Biology, University of Rome Tor Vergata, Rome, Italy, Department of Cell Biology, University of Calabria, Rende, Italy; Paoluzi, S., Department of Biology, University of Rome Tor Vergata, Rome, Italy; Castagnoli, L., Department of Biology, University of Rome Tor Vergata, Rome, Italy; Currell, B., Department of Molecular Biology, Genentech., South San Francisco, CA, United States; Seshagiri, S., Department of Molecular Biology, Genentech., South San Francisco, CA, United States; Yu, H., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Winsor, B., CNRS, Université de Strasbourg UMR7156, Génétique Moléculaire, Génomique et Microbiologie, Strasbourg, France; Vidal, M., Center for Cancer Systems Biology (CCSB), Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Gerstein, M.B., Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States, Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, United States, Department of Computer Science, Yale University, New Haven, CT, United States; Bader, G.D., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Volkmer, R., Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Cesareni, G., Department of Biology, University of Rome Tor Vergata, Rome, Italy, Research Institute Fondazione Santa Lucia, Rome, Italy; Drubin, D.G., Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States; Kim, P.M., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States; Sidhu, S.S., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Protein Engineering, Genentech., South San Francisco, CA, United States; Boone, C., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada","SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast twohybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes. © 2009 Tonikian et al.",,"protein SH3; actin binding protein; carrier protein; ligand; Lsb3 protein, S cerevisiae; peptide library; Saccharomyces cerevisiae protein; YSC84 protein, S cerevisiae; article; Bayes theorem; binding affinity; complex formation; controlled study; endocytosis; nonhuman; phage display; protein binding; protein domain; protein localization; protein protein interaction; Saccharomyces cerevisiae; algorithm; chemical structure; chemistry; gene expression regulation; genetics; metabolism; methodology; protein analysis; protein binding; Saccharomyces cerevisiae; Src homology domain; two hybrid system; Saccharomyces cerevisiae; Saccharomycetales; Algorithms; Bayes Theorem; Carrier Proteins; Endocytosis; Gene Expression Regulation, Fungal; Ligands; Microfilament Proteins; Models, Molecular; Peptide Library; Protein Binding; Protein Interaction Mapping; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; src Homology Domains; Two-Hybrid System Techniques",,"carrier protein, 80700-39-6; Carrier Proteins; Ligands; Lsb3 protein, S cerevisiae; Microfilament Proteins; Peptide Library; Saccharomyces cerevisiae Proteins; YSC84 protein, S cerevisiae",,,,"Pawson, T., Nash, P., Assembly of cell regulatory systems through protein interaction domains (2003) Science, 300 (5618), pp. 445-452. , DOI 10.1126/science.1083653; Tong, A.H.Y., Drees, B., Nardelli, G., Bader, G.D., Brannetti, B., Castagnoli, L., Evangelista, M., Cesareni, G., A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules (2002) Science, 295 (5553), pp. 321-324. , DOI 10.1126/science.1064987; Tonikian, R., Zhang, Y., Sazinsky, S.L., Currell, B., Yeh, J.H., A specificity map for the PDZ domain family (2008) PLoS Biol, 6, pp. e239. , doi:10.1371/journal.pbio.0060239; 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Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: A software Environment for integrated models of biomolecular interaction networks (2003) Genome Research, 13 (11), pp. 2498-2504. , DOI 10.1101/gr.1239303; Longtine, M.S., McKenzie III, A., Demarini, D.J., Shah, N.G., Wach, A., Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae (1998) Yeast, 14, pp. 953-961","Tonikian, R.; Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada",,,,,,,,15449173,,PBLIB,10.1371/journal.pbio.1000218,19841731,"English","PloS Biol.",Article,Scopus
"Merico D., Gfeller D., Bader G.D.","How to visually interpret biological data using networks",2009,"Nature Biotechnology",27,10,,921,924,,26,"http://www.scopus.com/inward/record.url?eid=2-s2.0-70349948795&partnerID=40&md5=a0d7cb756cd1a8e12667ba86f8a67f7f","Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, ON, Canada","Merico, D., Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, ON, Canada; Gfeller, D., Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, ON, Canada; Bader, G.D., Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, ON, Canada","Networks in biology can appear complex and difficult to decipher. We illustrate how to interpret biological networks with the help of frequently used visualization and analysis patterns. © 2009 Nature America, Inc.",,"Biological data; Biological networks; Visualization and analysis; Biology; protein; biology; chromosome; data analysis; data base; gene expression; gene interaction; mathematical model; methodology; priority journal; protein function; Saccharomyces cerevisiae; short survey; Data Interpretation, Statistical; Gene Regulatory Networks; Information Services; Metabolic Networks and Pathways; Models, Biological",,"protein, 67254-75-5",,,,"Pujana, M.A., (2007) Nat. Genet., 39, pp. 1338-1349; Mummery-Widmer, J.L., (2009) Nature, 458, pp. 987-992; Fraser, A.G., Marcotte, E.M., (2004) Nat. Genet., 36, pp. 559-564; Stark, C., (2006) Nucleic Acids Res., 34, pp. D535-D539; Hu, Z., (2007) Nucleic Acids Res., 35, pp. W625-632; Cline, M.S., (2007) Nat Protoc., 2, pp. 2366-2382; Ashburner, M., Gene ontology: Tool for the unification of biology (2000) The Gene Ontology Consortium. Nat. Genet., 25, pp. 25-29; Spellman, P.T., (1998) Mol Biol. Cell, 9, pp. 3273-3297; Gunsalus, K.C., (2005) Nature, 436, pp. 861-865; Hu, Z., (2007) Nat. Biotechnol., 25, pp. 547-554; Fukuda, K., Takagi, T., (2001) Bioinformatics, 17, pp. 829-837; Le Novère, N., (2009) Nat Biotechnol., 27, pp. 735-741; Strogatz, S.H., (2001) Nature, 410, pp. 268-276; Collins, S.R., (2007) Nature, 446, pp. 806-810; Reguly, T., (2006) J Biol., 5, p. 11; Davidson, E.H., (2002) Science, 295, pp. 1669-1678; Boone, C., Bussey, H., Andrews, B.J., (2007) Nat. Rev. Genet., 8, pp. 437-449; Stuart, J.M., Segal, E., Koller, D., Kim, S.K., (2003) Science, 302, pp. 249-255","Merico, D.; Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, ON, Canada",,,,,,,,10870156,,NABIF,10.1038/nbt.1567,19816451,"English","Nat. Biotechnol.",Short Survey,Scopus
"Ernst A., Sazinsky S.L., Hui S., Currell B., Dharsee M., Seshagiri S., Bader G.D., Sidhu S.S.","Rapid evolution of functional complexity in a domain family",2009,"Science Signaling",2,87,,,,,29,"http://www.scopus.com/inward/record.url?eid=2-s2.0-77949772254&partnerID=40&md5=4753a495166a1cf043ceba267d7932a5","Department of Protein Engineering, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E19-563, Cambridge, MA 02139, United States; Banting and Best Department of Medical Research, University of Toronto, Donnelly CCBR, 160 College Street, Toronto, ON M5S E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; Banting and Best Department of Medical Research, Department of Molecular Genetics, University of Toronto, Donnelly CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada","Ernst, A., Department of Protein Engineering, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States, Banting and Best Department of Medical Research, Department of Molecular Genetics, University of Toronto, Donnelly CCBR, 160 College Street, Toronto, ON M5S 3E1, Canada; Sazinsky, S.L., Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E19-563, Cambridge, MA 02139, United States; Hui, S., Banting and Best Department of Medical Research, University of Toronto, Donnelly CCBR, 160 College Street, Toronto, ON M5S E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Currell, B., Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; Dharsee, M., Banting and Best Department of Medical Research, University of Toronto, Donnelly CCBR, 160 College Street, Toronto, ON M5S E1, Canada; Seshagiri, S., Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; Bader, G.D., Banting and Best Department of Medical Research, University of Toronto, Donnelly CCBR, 160 College Street, Toronto, ON M5S E1, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Sidhu, S.S., Department of Protein Engineering, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States","Multicellular organisms rely on complex, fine-tuned protein networks to respond to environmental changes. We used in vitro evolution to explore the role of domain mutation and expansion in the evolution of network complexity. Using random mutagenesis to facilitate family expansion, we asked how versatile and robust the binding site must be to produce the rich functional diversity of the natural PDZ domain family. From a combinatorial protein library, we analyzed several hundred structured domain variants and found that one-quarter were functional for carboxyl-terminal ligand recognition and that our variant repertoire was as specific and diverse as the natural family. Our results show that ligand binding is hardwired in the PDZ fold and suggest that this flexibility may facilitate the rapid evolution of complex protein interaction networks. Copyright 2008 by the American Association for the Advancement of Science; all rights reserved.",,"epidermal growth factor receptor 2; ligand; scaffold protein; amino acid sequence; analytical research; article; binding site; carboxy terminal sequence; cell junction; DNA fingerprinting; evolution; family; functional assessment; gene library; genetic variability; in vitro study; ligand binding; mutagenesis; mutation; PDZ domain; peptide recognition module; postsynaptic membrane; priority journal; protein domain; protein interaction; protein stability; protein structure; structural gene; Adaptor Proteins, Signal Transducing; Animals; Binding Sites; Directed Molecular Evolution; Humans; Ligands; Mutagenesis; Protein Structure, Tertiary",,"epidermal growth factor receptor 2, 137632-09-8; Adaptor Proteins, Signal Transducing; ERBB2IP protein, human; Ligands",,,,"Pawson, T., Nash, P., Assembly of cell regulatory systems through protein interaction domains (2003) Science, 300, pp. 445-452; Lim, W.A., The modular logic of signaling proteins: Building allosteric switches from simple binding domains (2002) Curr. 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Cell Sci., 118, pp. 2093-2104; Hillier, B.J., Christopherson, K.S., Prehoda, K.E., Bredt, D.S., Lim, W.A., Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex (1999) Science, 284, pp. 812-815; G.D.B. acknowledges funding from the Canadian Institutes of Health Research (MOP-84324","Sidhu, S. S.; Department of Protein Engineering, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States; email: sachdev.sidhu@utoronto.ca",,,,,,,,19450877,,,10.1126/scisignal.2000416,19738200,"English","Sci. Signal.",Article,Scopus
"Tan C.S.H., Bodenmiller B., Pasculescu A., Jovanovic M., Hengartner M.O., Claus J., Bader G.D., Aebersold R., Pawson T., Linding R.","Comparative analysis reveals conserved protein phosphorylation networks implicated in multiple diseases",2009,"Science Signaling",2,81,,,,,83,"http://www.scopus.com/inward/record.url?eid=2-s2.0-70349526350&partnerID=40&md5=f2d184a10e6fe0ffaefd5885a25d39eb","Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH), 8093 Zurich, Switzerland; Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland; Institute for Systems Biology, Seattle, WA 98103, United States; Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, 8093 Zurich, Switzerland; Faculty of Science, University of Zurich, 8057 Zurich, Switzerland; Cellular and Molecular Logic Team, Section of Cell and Molecular Biology, Institute of Cancer Research (ICR), London SW3 6JB, United Kingdom","Tan, C.S.H., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Bodenmiller, B., Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH), 8093 Zurich, Switzerland; Pasculescu, A., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Jovanovic, M., Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland; Hengartner, M.O., Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland; Claus, J., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Bader, G.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Aebersold, R., Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH), 8093 Zurich, Switzerland, Institute for Systems Biology, Seattle, WA 98103, United States, Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, 8093 Zurich, Switzerland, Faculty of Science, University of Zurich, 8057 Zurich, Switzerland; Pawson, T., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Linding, R., Cellular and Molecular Logic Team, Section of Cell and Molecular Biology, Institute of Cancer Research (ICR), London SW3 6JB, United Kingdom","Protein kinases enable cellular information processing. Although numerous human phosphorylation sites and their dynamics have been characterized, the evolutionary history and physiological importance ofmany signaling events remain unknown. Using target phosphoproteomes determined with a similar experimental and computational pipeline, we investigated the conservation of human phosphorylation events in distantly related model organisms (fly, worm, and yeast). With a sequence-alignment approach, we identified 479 phosphorylation events in 344 human proteins that appear to be positionally conserved over ∼ 600 million years of evolution and hence are likely to be involved in fundamental cellular processes. This sequencealignment analysis suggested that many phosphorylation sites evolve rapidly and therefore do not display strong evolutionary conservation in terms of sequence position in distantly related organisms. Thus, we devised a network-alignment approach to reconstruct conserved kinase-substrate networks, which identified 778 phosphorylation events in 698 human proteins. Both methods identified proteins tightly regulated by phosphorylation as well as signal integration hubs, and both types of phosphoproteins were enriched in proteins encoded by disease-associated genes.We analyzed the cellular functions and structural relationships for these conserved signaling events, noting the incomplete nature of current phosphoproteomes. Assessing phosphorylation conservation at both site and network levels proved useful for exploring both fast-evolving and ancient signaling events. We reveal that multiple complex diseases seem to converge within the conserved networks, suggesting that disease development might rely on common molecular networks. Copyright 2008 by the American Association for the Advancement of Science; all rights reserved.",,"phosphoprotein; proteome; cyclin dependent kinase; cyclin dependent kinase activating kinase; cyclin-dependent kinase-activating kinase; protein; article; cell function; cell structure; clinical feature; comparative study; gene sequence; genetic conservation; nonhuman; priority journal; protein analysis; protein phosphorylation; signal transduction; amino acid sequence; animal; binding site; Caenorhabditis elegans; chemical structure; chemistry; classification; cluster analysis; disease predisposition; Drosophila melanogaster; genetics; human; metabolism; methodology; molecular evolution; molecular genetics; pathophysiology; phosphorylation; phylogeny; physiology; protein tertiary structure; proteomics; Saccharomyces cerevisiae; sequence homology; Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans; Cluster Analysis; Cyclin-Dependent Kinases; Disease Susceptibility; Drosophila melanogaster; Evolution, Molecular; Humans; Molecular Sequence Data; Molecular Structure; Phosphoproteins; Phosphorylation; Phylogeny; Protein Structure, Tertiary; Proteins; Proteomics; Saccharomyces cerevisiae; Sequence Homology, Amino Acid; Signal Transduction",,"cyclin dependent kinase, 150428-23-2; protein, 67254-75-5; Cyclin-Dependent Kinases, 2.7.1.37; Phosphoproteins; Proteins; cyclin-dependent kinase-activating kinase, 2.7.1.37",,,,"Hunt, T., Protein sequence motifs involved in recognition and targeting: A new series (1990) Trends Biochem. 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U.S.A, 77, pp. 1311-1315; Beltrao, P., Trinidad, J.C., Fiedler, D., Roguev, A., Lim, W.A., Shokat, K.M., Burlingame, A.L., Krogan, N.J., Evolution of phosphoregulation: Comparison of phosphorylation patterns across yeast species (2009) PLoS Biol., 7, pp. e1000134; Tan, C.S.H., Pasculescu, A., Lim, W.A., Pawson, T., Bader, G.D., Linding, R., Positive selection of tyrosine loss in metazoan evolution (2009) Science, , 9 July, (10.1126/science.1174301); Gnad, F., Ren, S., Cox, J., Olsen, J.V., MacEk, B., Oroshi, M., Mann, M., PHOSIDA (phosphorylation site database): Management, structural and evolutionary investigation, and prediction of phosphosites (2007) Genome Biol., 8, pp. R250; Fedorov, O., Marsden, B., Pogacic, V., Rellos, P., Müller, S., Bullock, A.N., Schwaller, J., Knapp, S., A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases (2007) Proc. Natl. Acad. Sci. U.S.A, 104, pp. 20523-20528; Louvet, C., Szot, G.L., Lang, J., Lee, M.R., Martinier, N., Bollag, G., Zhu, S., Bluestone, J.A., Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice (2008) Proc. Natl. Acad. Sci. U.S.A, 105, pp. 18895-18900; Pawson, T., Linding, R., Network medicine (2008) FEBS Lett., 582, pp. 1266-1270; Flicek, P., Aken, B.L., Beal, K., Ballester, B., Caccamo, M., Chen, Y., Clarke, L., Searle, S., Ensembl 2008 (2008) Nucleic Acids Res., 36, pp. D707-D714; Ward, J.J., Sodhi, J.S., McGuffin, L.J., Buxton, B.F., Jones, D.T., Prediction and functional analysis of native disorder in proteins from the three kingdoms of life (2004) J. Mol. Biol., 337, pp. 635-645; Maere, S., Heymans, K., Kuiper, M., BiNGO: A Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks (2005) Bioinformatics, 21, pp. 3448-3449; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res., 13, pp. 2498-2504; Hahn, W.C., Weinberg, R.A., Rules for making human tumor cells (2002) N. Engl. J. Med., 347, pp. 1593-1603; Vogelstein, B., Kinzler, K.W., Cancer genes and the pathways they control (2004) Nat. Med., 10, pp. 789-799; Mitelman, F., Recurrent chromosome aberrations in cancer (2000) Mutat. Res., 462, pp. 247-253; Futreal, P.A., Coin, L., Marshall, M., Down, T., Hubbard, T., Wooster, R., Rahman, N., Stratton, M.R., A census of human cancer genes (2004) Nat. Rev. Cancer, 4, pp. 177-183; Higgins, M.E., Claremont, M., Major, J.E., Sander, C., Lash, A.E., CancerGenes: A gene selection resource for cancer genome projects (2007) Nucleic Acids Res., 35, pp. D721-D726; Von Mering, C., Jensen, L.J., Kuhn, M., Chaffron, S., Doerks, T., Krüger, B., Snel, B., Bork, P., STRING 7-Recent developments in the integration and prediction of protein interactions (2007) Nucleic Acids Res., 35, pp. D358-D362; Hermanns, P., Bertuch, A.A., Bertin, T.K., Dawson, B., Schmitt, M.E., Shaw, C., Zabel, B., Lee, B., Consequences of mutations in the non-coding RMRP RNA in cartilage-hair hypoplasia (2005) Hum. Mol. Genet., 14, pp. 3723-3740; Linding, R., Jensen, L.J., Pasculescu, A., Olhovsky, M., Colwill, K., Bork, P., Yaffe, M.B., Pawson, T., NetworKIN: A resource for exploring cellular phosphorylation networks (2008) Nucleic Acids Res., 36, pp. D695-D699; note","Linding, R.; Cellular and Molecular Logic Team, Section of Cell and Molecular Biology, Institute of Cancer Research (ICR), London SW3 6JB, United Kingdom; email: linding@icr.ac.uk",,,,,,,,19450877,,,10.1126/scisignal.2000316,,"English","Sci. Signal.",Article,Scopus
"Yeung N., Cline M.S., Kuchinsky A., Smoot M.E., Bader G.D.","Exploring biological networks with cytoscape software",2008,"Current Protocols in Bioinformatics",,SUPPL. 23,,8.13.1,8.13.20,,10,"http://www.scopus.com/inward/record.url?eid=2-s2.0-58749115239&partnerID=40&md5=fe7326372204a8776f3f3efd5e5d9e42","University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada; Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA, United States; Agilent Technologies, Santa Clara, CA, United States; Department of Bioengineering, University of California, La Jolla, CA, United States","Yeung, N., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada; Cline, M.S., Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA, United States; Kuchinsky, A., Agilent Technologies, Santa Clara, CA, United States; Smoot, M.E., Department of Bioengineering, University of California, La Jolla, CA, United States; Bader, G.D., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada","Cytoscape is a free software package for visualizing, modeling, and analyzing molecular and genetic interaction networks. As a key feature, Cytoscape enables biologists to determine and analyze the interconnectivity of a list of genes or proteins. This unit explains how to use Cytoscape to load and navigate biological network information and view mRNA expression profiles and other functional genomics and proteomics data in the context of the network obtained for genes of interest. Additional analyses that can be performed with Cytoscape are also discussed. © 2008 by John Wiley & Sons, Inc.","Network analysis; Network visualization; Protein interactions biological network; Systems biology","messenger RNA; bioinformatics; computer interface; computer program; data base; functional genomics; functional proteomics; fungal genetics; gene expression profiling; gene interaction; gene regulatory network; information retrieval; molecular model; nonhuman; priority journal; review; Saccharomyces",,,"Cytoscape",,,"Bader, G.D., Hogue, C.W., An automated method for finding molecular complexes in large protein interaction networks (2003) BMC Bioinformatics, 4, p. 2. , http://www.biomedcentral.com/1471-2105/4/2; Bader, G., Donaldson, I., Wolting, C., Ouellette, B., Pawson, T., Hogue, C., BIND - The Biomolecular Interaction Network Database (2001) Nucleic Acids Res., 29, pp. 242-245; Bader, G.D., Cary, M.P., Sander, C., Pathguide: A pathway resource list (2006) Nucleic Acids Res., 34, pp. D504-D506; Cerami, E.G., Bader, G.D., Gross, B.E., Sander, C., cPath: Open source software for collecting, storing, and querying biological pathways (2006) BMC Bioinformatics, 7, p. 497. , http://www.biomedcentral.com/1471-2105/7/497; Christie, K.R., Weng, S., Balakrishnan, R., Costanzo, M.C., Dolinski, K., Dwight, S.S., Engel, S.R., Cherry, J.M., Saccharomyces Genome Database (SGD) provides tools to identify and analyze sequences from Saccharomyces cerevisiae and related sequences from other organisms (2004) Nucleic Acids Res., 32, pp. D311-D314; de Lichtenberg, U., Jensen, L.J., Brunak, S., Bork, P., Dynamic complex formation during the yeast cell cycle (2005) Science, 307, pp. 724-727; Garcia, O., Saveanu, C., Cline, M., Fromont-Racine, M., Jacquier, A., Schwikowski, B., Aittokallio, T., GOlorize: A Cytoscape plug-in for network visualization with Gene Ontology-based layout and coloring (2007) Bioinformatics, 23, pp. 394-396; Hermjakob, H., Montecchi-Palazzi, L., Lewington, C., Mudali, S., Kerrien, S., Orchard, S., Vingron, M., Apweiler, R., IntAct: An open source molecular interaction database (2004) Nucleic Acids Res., 32, pp. D452-D455; Ideker, T., Ozier, O., Schwikowski, B., Siegel, A.F., Discovering regulatory and signalling circuits in molecular interaction networks (2002) Bioinformatics, 18, pp. S233-S240; Joshi-Tope, G., Gillespie, M., Vastrik, I., D'Eustachio, P., Schmidt, E., de Bono, B., Jassal, B., Stein, L., Reactome: A knowledgebase of biological pathways (2005) Nucleic Acids Res., 33, pp. D428-D432; Krummenacker, M., Paley, S., Mueller, L., Yan, T., Karp, P.D., Querying and computing with BioCyc databases (2005) Bioinformatics, 21, pp. 3454-3455; Maere, S., Heymans, K., Kuiper, M., BiNGO: A Cytoscape plug-in to assess overrepresentation of gene ontology categories in biological networks (2005) Bioinformatics, 21, pp. 3448-3449; Morris, J.H., Huang, C.C., Babbitt, P.C., Ferrin, T.E., structureViz: Linking Cytoscape and UCSF Chimera (2007) Bioinformatics, 23, pp. 2345-2347; Peri, S., Navarro, J.D., Kristiansen, T.Z., Amanchy, R., Surendranath, V., Muthusamy, B., Gandhi, T.K., Suresh, S., Human protein reference database as a discovery resource for proteomics (2004) Nucleic Acids Res., 32, pp. D497-D501; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res., 13, pp. 2498-2504; Stuart, J.M., Segal, E., Koller, D., Kim, S.K., A gene-coexpression network for global discovery of conserved genetic modules (2003) Science, 302, pp. 249-255; Vailaya, A., Bluvas, P., Kincaid, R., Kuchinsky, A., Creech, M., Adler, A., An architecture for biological information extraction and representation (2005) Bioinformatics, 21, pp. 430-438; Wixon, J., Kell, D., The Kyoto encyclopedia of genes and genomes - KEGG (2000) Yeast, 17, pp. 48-55; Xenarios, I., Salẃýnski, L., Duan, X., Higney, P., Kim, S.M., Eisenberg, D., DIP, the Database of Interacting Proteins: Aresearch tool for studying cellular networks of protein interactions (2002) Nucleic Acids Res., 30, pp. 303-305; Yu, H., Kim, P.M., Sprecher, E., Trifonov, V., Gerstein, M., The importance of bottlenecks in protein networks: Correlation with gene essentiality and expression dynamics (2007) PLoS Comput. Biol., 3, pp. e59. , http://www.ploscompbiol.org/article/ info%3Adoi%2F10.1371%2Fjournal.pcbi.0030059; Zanzoni, A., Montecchi-Palazzi, L., Quondam, M., Ausiello, G., Helmer-Citterich, M., Cesareni, G., MINT: A Molecular INTeraction database (2002) FEBS Lett., 513, pp. 135-140","Yeung, N.; University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, ON, Canada",,,,,,,,19343396,,,10.1002/0471250953.bi0813s23,,"English","Curr. Protoc. Bioinform.",Review,Scopus
"Tonikian R., Zhang Y., Sazinsky S.L., Currell B., Yeh J.H., Reva B., Held H.A., Appleton B.A., Evangelista M., Wu Y., Xin X., Chan A.C., Seshagiri S., Lasky L.A., Sander C., Boone C., Bader G.D., Sidhu S.S.","A specificity map for the PDZ domain family.",2008,"PLoS biology",6,9,,,,,68,"http://www.scopus.com/inward/record.url?eid=2-s2.0-55749111046&partnerID=40&md5=9280a21ee56fc9729f02045953303270","Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.","Tonikian, R., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Zhang, Y., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Sazinsky, S.L., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Currell, B., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Yeh, J.H., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Reva, B., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Held, H.A., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Appleton, B.A., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Evangelista, M., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Wu, Y., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Xin, X., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Chan, A.C., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Seshagiri, S., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Lasky, L.A., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Sander, C., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Boone, C., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Bader, G.D., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.; Sidhu, S.S., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.","PDZ domains are protein-protein interaction modules that recognize specific C-terminal sequences to assemble protein complexes in multicellular organisms. By scanning billions of random peptides, we accurately map binding specificity for approximately half of the over 330 PDZ domains in the human and Caenorhabditis elegans proteomes. The domains recognize features of the last seven ligand positions, and we find 16 distinct specificity classes conserved from worm to human, significantly extending the canonical two-class system based on position -2. Thus, most PDZ domains are not promiscuous, but rather are fine-tuned for specific interactions. Specificity profiling of 91 point mutants of a model PDZ domain reveals that the binding site is highly robust, as all mutants were able to recognize C-terminal peptides. However, many mutations altered specificity for ligand positions both close and far from the mutated position, suggesting that binding specificity can evolve rapidly under mutational pressure. Our specificity map enables the prediction and prioritization of natural protein interactions, which can be used to guide PDZ domain cell biology experiments. Using this approach, we predicted and validated several viral ligands for the PDZ domains of the SCRIB polarity protein. These findings indicate that many viruses produce PDZ ligands that disrupt host protein complexes for their own benefit, and that highly pathogenic strains target PDZ domains involved in cell polarity and growth.",,"Caenorhabditis elegans protein; membrane protein; peptide; proteome; SCRIB protein, human; tumor suppressor protein; virus protein; amino acid sequence; animal; article; binding site; chemical structure; chemistry; classification; genetics; human; metabolism; molecular genetics; mutation; PDZ domain; phylogeny; protein secondary structure; Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans Proteins; Humans; Membrane Proteins; Models, Molecular; Molecular Sequence Data; Mutation; PDZ Domains; Peptides; Phylogeny; Protein Structure, Secondary; Proteome; Tumor Suppressor Proteins; Viral Proteins",,"Caenorhabditis elegans Proteins; Membrane Proteins; Peptides; Proteome; SCRIB protein, human; Tumor Suppressor Proteins; Viral Proteins",,,,,"Tonikian, R.",,,,,,,,15457885,,,10.1371/journal.pbio.0060239,18828675,"English","PLoS Biol.",Article,Scopus
"Yeung N., Cline M.S., Kuchinsky A., Smoot M.E., Bader G.D.","Exploring biological networks with Cytoscape software.",2008,"Current protocols in bioinformatics / editoral board, Andreas D. Baxevanis ... [et al.]",Chapter 8,,,,,,4,"http://www.scopus.com/inward/record.url?eid=2-s2.0-55249083549&partnerID=40&md5=c13f0ae27a31458440a27cc79a60ebcc","University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.","Yeung, N., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.; Cline, M.S., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.; Kuchinsky, A., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.; Smoot, M.E., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.; Bader, G.D., University of Toronto, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.","Cytoscape is a free software package for visualizing, modeling, and analyzing molecular and genetic interaction networks. As a key feature, Cytoscape enables biologists to determine and analyze the interconnectivity of a list of genes or proteins. This unit explains how to use Cytoscape to load and navigate biological network information and view mRNA expression profiles and other functional genomics and proteomics data in the context of the network obtained for genes of interest. Additional analyses that can be performed with Cytoscape are also discussed. (c) 2008 by John Wiley & Sons, Inc.",,"animal; article; biology; computer program; computer simulation; data base; gene expression profiling; gene regulatory network; genomics; human; methodology; proteomics; quantitative structure activity relation; utilization review; Animals; Computational Biology; Computer Simulation; Database Management Systems; Gene Expression Profiling; Gene Regulatory Networks; Genomics; Humans; Proteomics; Quantitative Structure-Activity Relationship; Software",,,,,,,"Yeung, N.",,,,,,,,1934340X,,,,18819078,"English","Curr Protoc Bioinformatics",Article,Scopus
"Tonikian R., Zhang Y., Sazinsky S.L., Currell B., Yeh J.-H., Reva B., Held H.A., Appleton B.A., Evangelista M., Wu Y., Xin X., Chan A.C., Seshagiri S., Lasky L.A., Sander C., Boone C., Bader G.D., Sidhu S.S.","A specificity map for the PDZ domain family",2008,"PLoS Biology",6,9, e239,2043,2059,,80,"http://www.scopus.com/inward/record.url?eid=2-s2.0-54749086397&partnerID=40&md5=0ecb32128c66ec4667c877716155976f","Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Protein Engineering, Genentech, South San Francisco, CA, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Molecular Biology, Genentech, South San Francisco, CA, United States; Department of Immunology, Genentech, South San Francisco, CA, United States; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Department of Antibody Engineering, Genentech, South San Francisco, CA, United States","Tonikian, R., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Zhang, Y., Department of Protein Engineering, Genentech, South San Francisco, CA, United States; Sazinsky, S.L., Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States; Currell, B., Department of Molecular Biology, Genentech, South San Francisco, CA, United States; Yeh, J.-H., Department of Immunology, Genentech, South San Francisco, CA, United States; Reva, B., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Held, H.A., Department of Protein Engineering, Genentech, South San Francisco, CA, United States; Appleton, B.A., Department of Protein Engineering, Genentech, South San Francisco, CA, United States; Evangelista, M., Department of Molecular Biology, Genentech, South San Francisco, CA, United States; Wu, Y., Department of Antibody Engineering, Genentech, South San Francisco, CA, United States; Xin, X., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Chan, A.C., Department of Immunology, Genentech, South San Francisco, CA, United States; Seshagiri, S., Department of Molecular Biology, Genentech, South San Francisco, CA, United States; Lasky, L.A., Department of Protein Engineering, Genentech, South San Francisco, CA, United States; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Boone, C., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Bader, G.D., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Sidhu, S.S., Terrence Donnelly Center for Cellular and Biomolecular Research, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada, Department of Protein Engineering, Genentech, South San Francisco, CA, United States","PDZ domains are protein-protein interaction modules that recognize specific C-terminal sequences to assemble protein complexes in multicellular organisms. By scanning billions of random peptides, we accurately map binding specificity for approximately half of the over 330 PDZ domains in the human and Caenorhabditis elegans proteomes. The domains recognize features of the last seven ligand positions, and we find 16 distinct specificity classes conserved from worm to human, significantly extending the canonical two-class system based on position -2. Thus, most PDZ domains are not promiscuous, but rather are fine-tuned for specific interactions. Specificity profiling of 91 point mutants of a model PDZ domain reveals that the binding site is highly robust, as all mutants were able to recognize C-terminal peptides. However, many mutations altered specificity for ligand positions both close and far from the mutated position, suggesting that binding specificity can evolve rapidly under mutational pressure. Our specificity map enables the prediction and prioritization of natural protein interactions, which can be used to guide PDZ domain cell biology experiments. Using this approach, we predicted and validated several viral ligands for the PDZ domains of the SCRIB polarity protein. 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"Ashkenazi M., Bader G.D., Kuchinsky A., Moshelion M., States D.J.","Cytoscape ESP: Simple search of complex biological networks",2008,"Bioinformatics",24,12,,1465,1466,,7,"http://www.scopus.com/inward/record.url?eid=2-s2.0-45449103076&partnerID=40&md5=3c692520f1deb3619c63b67df21752d8","Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Hebrew University of Jerusalem, Rehovot, Israel; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Agilent Technologies, Santa Clara, CA, United States; Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, United States","Ashkenazi, M., Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Hebrew University of Jerusalem, Rehovot, Israel; Bader, G.D., Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Kuchinsky, A., Agilent Technologies, Santa Clara, CA, United States; Moshelion, M., Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Hebrew University of Jerusalem, Rehovot, Israel; States, D.J., Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, United States","Summary: Cytoscape enhanced search plugin (ESP) enables searching complex biological networks on multiple attribute fields using logical operators and wildcards. Queries use an intuitive syntax and simple search line interface. ESP is implemented as a Cytoscape plugin and complements existing search functions in the Cytoscape network visualization and analysis software, allowing users to easily identify nodes, edges and subgraphs of interest, even for very large networks. © The Author 2008. Published by the Oxford University Press. All rights reserved.",,"aquaporin; article; computer analysis; computer program; data analysis; gene expression; gene regulatory network; imaging system; information processing; information retrieval; molecular interaction; nonhuman; osmotic stress; plant physiology; priority journal; systems biology; water transport; Algorithms; Computer Graphics; Computer Simulation; Information Storage and Retrieval; Models, Biological; Signal Transduction; Software; User-Computer Interface",,"aquaporin, 215587-75-0","Cytoscape",,,"Boursiac, Y., Early effects of salinity on water transport in Arabidopsis roots. Molecular and cellular features of Aquaporin expression (2005) Plant Physiol, 139, pp. 790-805; Hermjakob, H., IntAct: An open source molecular interaction database (2004) Nucleic Acids Res, 32, pp. D452-D455; Jayapandian, M., Michigan molecular interactions (MiMI): Putting the jigsaw puzzle together (2007) Nucleic Acids Res, 35, pp. D566-D571; Kilian, J., The AtGenExpress global stress expression data set: Protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses (2007) Plant J, 50, pp. 347-363; Shannon, P., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504. , http://www.cytoscape.org, Available at; Suzuki, N., Enhanced tolerance to environmental stress in transgenic plants expressing the transcriptional coactivator multiprotein bridging factor lc (2005) Plant Physiol, 139, pp. 1313-1322; Wang, W., Plant responses to drought, salinity and extreme temperatures: Towards genetic engineering for stress tolerance (2003) Planta, 218, pp. 1-14; Xenarios, I., DIP, the database of interacting proteins: A research tool for studying cellular networks of protein interactions (2002) Nucleic Acids Res, 30, pp. 303-305","Ashkenazi, M.; Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture, Hebrew University of Jerusalem, Rehovot, Israel; email: ashkenaz@agri.huji.ac.il",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/btn208,18445605,"English","Bioinformatics",Article,Scopus
"Skrabanek L., Saini H.K., Bader G.D., Enright A.J.","Computational prediction of protein-protein interactions",2008,"Molecular Biotechnology",38,1,,1,17,,60,"http://www.scopus.com/inward/record.url?eid=2-s2.0-38949138554&partnerID=40&md5=9cec43b3b15f5eb79b24fc905537455c","Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, United States; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada","Skrabanek, L., Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, United States; Saini, H.K., Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; Bader, G.D., Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Enright, A.J., Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom","Recently a number of computational approaches have been developed for the prediction of protein-protein interactions. Complete genome sequencing projects have provided the vast amount of information needed for these analyses. These methods utilize the structural, genomic, and biological context of proteins and genes in complete genomes to predict protein interaction networks and functional linkages between proteins. Given that experimental techniques remain expensive, time-consuming, and labor-intensive, these methods represent an important advance in proteomics. Some of these approaches utilize sequence data alone to predict interactions, while others combine multiple computational and experimental datasets to accurately build protein interaction maps for complete genomes. These methods represent a complementary approach to current high-throughput projects whose aim is to delineate protein interaction maps in complete genomes. We will describe a number of computational protocols for protein interaction prediction based on the structural, genomic, and biological context of proteins in complete genomes, and detail methods for protein interaction network visualization and analysis. © 2007 Humana Press Inc.","Gene fusion; Gene neighborhood; Genome context; Phylogenetic profiles; Protein interaction networks; Visualization","Computational methods; Data reduction; Data structures; Genes; Visualization; Gene fusion; Gene neighborhood; Phylogenetic profiles; Protein interaction networks; Proteins; bacterial protein; multiprotein complex; Bayes theorem; computer model; gene expression; gene fusion; gene interaction; genome; phylogeny; protein DNA interaction; protein localization; protein protein interaction; protein tertiary structure; proteomics; review; biotechnology; chemical structure; computer program; computer simulation; genetic database; genomics; protein analysis; protein microarray; statistics; two hybrid system; Biotechnology; Computer Simulation; Databases, Genetic; Gene Fusion; Genomics; Models, Molecular; Multiprotein Complexes; Phylogeny; Protein Array Analysis; Protein Interaction Mapping; Proteomics; Software; Two-Hybrid System Techniques",,"Multiprotein Complexes",,,,"Mendelsohn, A.R., Brent, R., Protein interaction methods-toward an endgame (1999) Science, 284, pp. 1948-1950. , 5422; Eisenberg, D., Marcotte, E.M., Xenarios, I., Yeates, T.O., Protein function in the post-genomic era (2000) Nature, 405, pp. 823-826. , 6788; Huynen, M., Snel, B., Lathe, W., Bork, P., Exploitation of gene context (2000) Current Opinion in Structural Biology, 10, pp. 366-370. , 3; Grigoriev, A., A relationship between gene expression and protein interactions on the proteome scale: Analysis of the bacteriophage T7 and the yeast Saccharomyces cerevisiae (2001) Nucleic Acids Research, 29, pp. 3513-3519. , 17; Ge, H., Liu, Z., Church, G.M., Vidal, M., Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae (2001) Nature Genetics, 29, pp. 482-486. , 4; Jansen, R., Greenbaum, D., Gerstein, M., Relating whole-genome expression data with protein-protein interactions (2002) Genome Research, 12, pp. 37-46. , 1; Marcotte, E.M., Pellegrini, M., Thompson, M.J., Yeates, T.O., Eisenberg, D., A combined algorithm for genome-wide prediction of protein function (1999) Nature, 402, pp. 83-86. , 6757; Jansen, R., Yu, H., Greenbaum, D., Kluger, Y., Krogan, N.J., Chung, S., Emili, A., Gerstein, M., A Bayesian networks approach for predicting protein-protein interactions from genomic data (2003) Science, 302, pp. 449-453. , 5644; Sussman, J.L., Lin, D., Jiang, J., Manning, N.O., Prilusky, J., Ritter, O., Abola, E.E., Protein Data Bank (PDB): Database of three-dimensional structural information of biological macromolecules (1998) Acta Crystallographica. 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J.; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; email: aje@sanger.ac.uk",,,,,,,,10736085,,,10.1007/s12033-007-0069-2,18095187,"English","Mol. Biotechnol.",Review,Scopus
"Cline M.S., Smoot M., Cerami E., Kuchinsky A., Landys N., Workman C., Christmas R., Avila-Campilo I., Creech M., Gross B., Hanspers K., Isserlin R., Kelley R., Killcoyne S., Lotia S., Maere S., Morris J., Ono K., Pavlovic V., Pico A.R., Vailaya A., Wang P.L., Adler A., Conklin B.R., Hood L., Kuiper M., Sander C., Schmulevich I., Schwikowski B., Warner G.J., Ideker T., Bader G.D.","Integration of biological networks and gene expression data using Cytoscape.",2007,"Nature protocols",2,10,,2366,2382,,477,"http://www.scopus.com/inward/record.url?eid=2-s2.0-38449101120&partnerID=40&md5=55534c45f4bde360c31b803dc4b9cfbd","Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.","Cline, M.S., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Smoot, M., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Cerami, E., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Kuchinsky, A., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Landys, N., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Workman, C., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Christmas, R., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Avila-Campilo, I., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Creech, M., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Gross, B., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Hanspers, K., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Isserlin, R., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Kelley, R., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Killcoyne, S., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Lotia, S., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Maere, S., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Morris, J., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Ono, K., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Pavlovic, V., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Pico, A.R., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Vailaya, A., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Wang, P.L., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Adler, A., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Conklin, B.R., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Hood, L., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Kuiper, M., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Sander, C., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Schmulevich, I., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Schwikowski, B., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Warner, G.J., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Ideker, T., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.; Bader, G.D., Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris cedex 15, France.","Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.",,"messenger RNA; article; biology; computer program; gene expression profiling; gene regulatory network; genomics; metabolism; methodology; proteomics; Computational Biology; Gene Expression Profiling; Gene Regulatory Networks; Genomics; Proteomics; RNA, Messenger; Software",,"RNA, Messenger",,,,,"Cline, M.S.",,,,,,,,17502799,,,10.1038/nprot.2007.324,17947979,"English","Nat Protoc",Article,Scopus
"Zogopoulos G., Ha K.C.H., Naqib F., Moore S., Kim H., Montpetit A., Robidoux F., Laflamme P., Cotterchio M., Greenwood C., Scherer S.W., Zanke B., Hudson T.J., Bader G.D., Gallinger S.","Germ-line DNA copy number variation frequencies in a large North American population",2007,"Human Genetics",122,3-4,,345,353,,94,"http://www.scopus.com/inward/record.url?eid=2-s2.0-35448992970&partnerID=40&md5=67e64d2604763fb82c916b357909d209","Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada; Dr. Zane Cohen Digestive Diseases Clinical Research Centre, Mount Sinai Hospital, Toronto, ON, Canada; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; The McGill University, Genome Québec Innovation Centre, Montreal, QC, Canada; Cancer Care Ontario, Toronto, ON, Canada; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Hospital for Sick Children, Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada; Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5, Canada; Samuel Lunenfeld Research Institute, Toronto, ON, Canada","Zogopoulos, G., Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada, Dr. Zane Cohen Digestive Diseases Clinical Research Centre, Mount Sinai Hospital, Toronto, ON, Canada; Ha, K.C.H., Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada, Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Naqib, F., Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada, Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Moore, S., Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada; Kim, H., Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada; Montpetit, A., The McGill University, Genome Québec Innovation Centre, Montreal, QC, Canada; Robidoux, F., The McGill University, Genome Québec Innovation Centre, Montreal, QC, Canada; Laflamme, P., The McGill University, Genome Québec Innovation Centre, Montreal, QC, Canada; Cotterchio, M., Cancer Care Ontario, Toronto, ON, Canada; Greenwood, C., Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; Scherer, S.W., The Hospital for Sick Children, Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada; Zanke, B., Ontario Institute for Cancer Research, Toronto, ON, Canada; Hudson, T.J., Ontario Institute for Cancer Research, Toronto, ON, Canada; Bader, G.D., Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5, Canada; Gallinger, S., Sam Minuk Cancer Genetics and Biomarker Laboratories, Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, ON, Canada, Dr. Zane Cohen Digestive Diseases Clinical Research Centre, Mount Sinai Hospital, Toronto, ON, Canada, Cancer Care Ontario, Toronto, ON, Canada, Samuel Lunenfeld Research Institute, Toronto, ON, Canada","Genomic copy number variation (CNV) is a recently identified form of global genetic variation in the human genome. The Affymetrix GeneChip 100 and 500 K SNP genotyping platforms were used to perform a large-scale population-based study of CNV frequency. We constructed a genomic map of 578 CNV regions, covering approximately 220 Mb (7.3%) of the human genome, identifying 183 previously unknown intervals. Copy number changes were observed to occur infrequently (<1%) in the majority (>93%) of these genomic regions, but encompass hundreds of genes and disease loci. This North American population-based map will be a useful resource for future genetic studies. © Springer-Verlag 2007.",,"adult; aged; article; controlled study; DNA structure; female; gene frequency; gene mapping; gene number; genetic analysis; genetic variability; genotype; human; human cell; male; North America; population genetics; priority journal; single nucleotide polymorphism; Aged; Chromosome Mapping; DNA; Female; Gene Dosage; Gene Frequency; Genetics, Population; Genome, Human; Germ Cells; Humans; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Ontario; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Registries; Variation (Genetics)",,"DNA, 9007-49-2",,,,"Aitman, T.J., Dong, R., Vyse, T.J., Norsworthy, P.J., Johnson, M.D., Smith, J., Mangion, J., Cook, H.T., Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans (2006) Nature, 439, pp. 851-855; Berciano, J., Calleja, J., Combarros, O., Charcot-Marie-Tooth disease (1994) Neurology, 44, pp. 1985-1986; 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Freeman, J.L., Perry, G.H., Feuk, L., Redon, R., McCarroll, S.A., Altshuler, D.M., Aburatani, H., Lee, C., Copy number variation: New insights in genome diversity (2006) Genome Res, 8, pp. 949-961; Gonzalez, E., Kulkarni, H., Bolivar, H., Mangano, A., Sanchez, R., Catano, G., Nibbs, R.J., Ahuja, S.K., The influence of CCL3L1 gene-containing segmental duplications on HIV-1/ AIDS susceptibility (2005) Science, 307, pp. 1434-1440; Hamosh, A., Scott, A.F., Amberger, J., Bocchini, C., Valle, D., McKusick, V.A., Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders (2006) Nucleic Acids Res, 30, pp. 52-55; Higgins, M.E., Claremount, M., Major, J.E., Sander, C., Lash, A.E., Cancer Genes: A gene selection resource for cancer genome projects (2006) Nucleic Acids Res, 35, pp. D721-D726; Hinds, D.A., Kloek, A.P., Jen, M., Chen, X., Frazer, K.A., Common deletions and SNPs are in linkage disequilibrium in the human genome (2006) Nat Genet, 38, pp. 82-85; Hua, J., Craig, D.W., Brun, M., Webster, J., Zismann, V., Tembe, W., Joshipura, K., Stephan, D.A., SNiPer-HD: Improved genotype calling accuracy by an expectation-maximization algorithm for high-density SNP arrays (2007) Bioinformatics, 23, pp. 57-63; Huang, J., Wei, W., Chen, J., Zhang, J., Liu, G., Di, X., Mei, R., Shapero, M.H., CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays (2006) BMC Bioinformatics, 7, p. 83; Iafrate, A.J., Feuk, L., Rivera, M.N., Listewnik, M.L., Donahoe, P.K., Qi, Y., Scherer, S.W., Lee, C., Detection of large-scale variation in the human genome (2004) Nat Genet, 36, pp. 949-951; Karolchik, D., Baertsch, R., Diekhans, M., Furey, T.S., Hinrichs, A., Lu, Y.T., Roskin, K.M., Kent, W.J., The UCSC Genome Browser Database (2003) Nucleic Acids Res, 31, pp. 51-54; Karolchik, D., Hinrichs, A.S., Furey, T.S., Roskin, K.M., Sugnet, C.W., Haussler, D., Kent, W.J., The UCSC Table Browser data retrieval tool (2004) Nucleic Acids Res, 32, pp. D493-D496; Kent, W.J., Sugnet, C.W., Furey, T.S., Roskin, K.M., Pringle, T.H., Zahler, A.M., Haussler, D., The human genome browser at UCSC (2002) Genome Res, 12, pp. 996-1006; Le Marechal, C., Masson, E., Chen, J.M., Morel, F., Ruszniewski, P., Levy, P., Ferec, C., Hereditary pancreatitis caused by triplication of the trypsinogen locus (2006) Nat Genet, 38, pp. 1372-1374; Lee, J.A., Lupski, J.R., Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders (2006) Neuron, 52, pp. 103-121; McCarroll, S., Hadnott, T.H., Perry, G.H., Sabeti, P.C., Zody, M.C., Barrett, J.C., Dallaire, S., Altshuler, D.M., Common deletion polymorphisms in the human genome (2006) Nat Genet, 38, pp. 86-92. , The International HapMap Consortium; Nannya, Y., Sanada, M., Nakazaki, K., Hosoya, N., Wang, L., Hangaishi, A., Kurokawa, M., Ogawa, S., A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays (2005) Cancer Res, 65, pp. 6071-6079; Redon, R., Ishikawa, S., Fitch, K.R., Feuk, L., Perry, G.H., Andrews, T.D., Fiegler, H., Global variation in copy number in the human genome (2006) Nature, 444, pp. 444-454; Sebat, J., Lakshmi, B., Troge, J., Alexander, J., Young, J., Lundin, P., Maner, S., Wigler, M., Large-scale copy number polymorphism in the human genome (2004) Science, 305, pp. 525-528; Sharp, A.J., Locke, D.P., McGrath, S.D., Cheng, Z., Bailey, J.A., Vallente, R.U., Pertz, L.M., Eichler, E.E., Segmental duplications and copy-number variation in the human genome (2005) Am J Hum Genet, 77, pp. 78-88; Sjoblom, T., Jones, S., Wood, L.D., Parsons, D.W., Lin, J., Barber, T.D., Mandelker, D., The consensus coding sequences of human breast and colorectal cancers (2006) Science, 314, pp. 268-274; Tuzun, E., Sharp, A.J., Bailey, J.A., Kaul, R., Morrison, V.A., Pertz, L.M., Haugen, E., Eichler, E.E., Fine-scale structural variation of the human genome (2005) Nat Genet, 37, pp. 727-732; Wong, K.K., deLeeuw, R.J., Dosanjh, N.S., Kimm, L.R., Cheng, Z., Horsman, D.E., MacAulay, C., Lam, W.L., A comprehensive analysis of common copy-number variations in the human genome (2007) Am J Hum Genet, 80, pp. 91-104","Gallinger, S.; Samuel Lunenfeld Research Institute, Toronto, ON, Canada; email: sgallinger@mtsinai.on.ca",,,,,,,,03406717,,HUGED,10.1007/s00439-007-0404-5,17638019,"English","Hum. Genet.",Article,Scopus
"Kerrien S., Orchard S., Montecchi-Palazzi L., Aranda B., Quinn A.F., Vinod N., Bader G.D., Xenarios I., Wojcik J., Sherman D., Tyers M., Salama J.J., Moore S., Ceol A., Chatr-Aryamontri A., Oesterheld M., Stumpflen V., Salwinski L., Nerothin J., Cerami E., Cusick M.E., Vidal M., Gilson M., Armstrong J., Woollard P., Hogue C., Eisenberg D., Cesareni G., Apweiler R., Hermjakob H.","Broadening the horizon - Level 2.5 of the HUPO-PSI format for molecular interactions",2007,"BMC Biology",5,, 44,,,,92,"http://www.scopus.com/inward/record.url?eid=2-s2.0-35348976204&partnerID=40&md5=1a8d704c62886b2fbf8664e57e3dfe7f","European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Banting and Best Department of Medical, Research and Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada; Merck Serono, 9 chemin des Mines, 1211 Geneva, Switzerland; Laboratoire Bordelais de Recherche en Informatique, ENSI Électronique, Informatique et Radiocomm de Bordeaux, Bordeaux, France; The Blueprint Initiative of Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; National University of Singapore, Office of Life Sciences (OLS), Centre for Life Sciences, Singapore, Singapore; Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy; Institute for Bioinformatics, GSF - National Research Center for Environment and Health, Neuherberg, Germany; UCLA-DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA, United States; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, Box 460, New York, NY, United States; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States; Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD, United States; Glaxo Smithkline Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts, United Kingdom; Dept. of Biochemistry, University of Toronto, Toronto, ON, Canada","Kerrien, S., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Orchard, S., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Montecchi-Palazzi, L., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Aranda, B., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Quinn, A.F., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Vinod, N., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Bader, G.D., Banting and Best Department of Medical, Research and Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada; Xenarios, I., Merck Serono, 9 chemin des Mines, 1211 Geneva, Switzerland; Wojcik, J., Merck Serono, 9 chemin des Mines, 1211 Geneva, Switzerland; Sherman, D., Laboratoire Bordelais de Recherche en Informatique, ENSI Électronique, Informatique et Radiocomm de Bordeaux, Bordeaux, France; Tyers, M., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada; Salama, J.J., The Blueprint Initiative of Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Moore, S., The Blueprint Initiative of Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada, National University of Singapore, Office of Life Sciences (OLS), Centre for Life Sciences, Singapore, Singapore; Ceol, A., Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy; Chatr-Aryamontri, A., Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy; Oesterheld, M., Institute for Bioinformatics, GSF - National Research Center for Environment and Health, Neuherberg, Germany; Stümpflen, V., Institute for Bioinformatics, GSF - National Research Center for Environment and Health, Neuherberg, Germany; Salwinski, L., UCLA-DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA, United States; Nerothin, J., UCLA-DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA, United States; Cerami, E., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, Box 460, New York, NY, United States; Cusick, M.E., Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States; Vidal, M., Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States; Gilson, M., Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD, United States; Armstrong, J., Glaxo Smithkline Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts, United Kingdom; Woollard, P., Glaxo Smithkline Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts, United Kingdom; Hogue, C., Dept. of Biochemistry, University of Toronto, Toronto, ON, Canada; Eisenberg, D., UCLA-DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA, United States; Cesareni, G., Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy; Apweiler, R., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Hermjakob, H., European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom","Background: Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. Results: The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. Conclusion: The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel. © 2007 Kerrien et al; licensee BioMed Central Ltd.",,"chemical agent; chemical compound; nucleic acid; protein; access to information; article; automation, computers and data processing; biological activity; computer system; data analysis; data analysis software; data synthesis; health care organization; information processing; information technology; molecular computer; molecular interaction; molecular mechanics; program development; protein analysis; protein protein interaction; reference database; biology; computer graphics; computer interface; data base; methodology; natural language processing; protein analysis; protein database; proteomics; standard; Computational Biology; Computer Graphics; Database Management Systems; Databases, Protein; Natural Language Processing; Protein Interaction Mapping; Proteomics; User-Computer Interface",,"protein, 67254-75-5",,,,"Hermjakob, H., Montecchi-Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., Ceol, A., Moore, S., von Mering, C., The HUPO PSI's molecular interaction format - A community standard for the representation of protein interaction data (2004) Nat Biotechnol, 22, pp. 177-183. , 10.1038/nbt926 14755292; Alfarano, C., Andrade, C.E., Anthony, K., Bahroos, N., Bajec, M., Bantoft, K., Betel, D., Burgess, E., The Biomolecular Interaction Network Database and related tools 2005 update (2005) Nucleic Acids Res, 33, pp. D418-424. , 540005 15608229 10.1093/nar/gki051; Salwinski, L., Miller, C.S., Smith, A.J., Pettit, F.K., Bowie, J.U., Eisenberg, D., The Database of Interacting Proteins: 2004 update (2004) Nucleic Acids Res, 32, pp. D449-D451. , 14681454 10.1093/nar/gkh086; Kerrien, S., Alam-Faruque, Y., Aranda, B., Bancarz, I., Bridge, A., Derow, C., Dimmer, E., Huntley, R., IntAct - Open source resource for molecular interaction data (2007) Nucleic Acids Res, 35, pp. D561-D565. , 1751531 17145710 10.1093/nar/gkl958; Chatr-Aryamontri, A., Ceol, A., Palazzi, L.M., Nardelli, G., Schneider, M.V., Castagnoli, L., Cesareni, G., MINT: The Molecular INTeraction database (2007) Nucleic Acids Res, 35, pp. D572-D574. , 1751541 17135203 10.1093/nar/gkl950; Guldener, U., Munsterkotter, M., Oesterheld, M., Pagel, P., Ruepp, A., Mewes, H.W., Stumpflen, V., MPact: The MIPS protein interaction resource on yeast (2006) Nucleic Acids Res, 34, pp. D436-D441. , 1347366 16381906 10.1093/nar/gkj003; Hybrigenics, , http://www.hybrigenics.fr; The HUPO Proteomics Standards Initiative, Molecular Interaction Work Group, , http://www.psidev.info/index.php?q=node/60; Bradshaw, R.A., Burlingame, A.L., Carr, S., Aebersold, R., Reporting protein identification data: The next generation of guidelines (2006) Mol Cell Proteomics, 5, pp. 787-788. , 10.1074/mcp.E600005-MCP200 16670253; Wilkins, M.R., Appel, R.D., Van Eyk, J.E., Chung, M.C., Gorg, A., Hecker, M., Huber, L.A., Paik, Y.K., Guidelines for the next 10 years of proteomics (2006) Proteomics, 6, pp. 4-8. , 10.1002/pmic.200500856 16400714; Jones, A.R., Pizarro, A., Spellman, P., Miller, M., FuGE: Functional Genomics Experiment Object Model (2006) OMICS, 10, pp. 179-184. , 10.1089/omi.2006.10.179 16901224; Open Biomedical Ontologies, , http://obo.sf.net; The IntAct Validator, , http://www.ebi.ac.uk/intact/validator; The HUPO Proteomics Standards Initiative, , http://www.psidev.info; BioPAX, , http://www.biopax.org; BioPAX Wiki, , http://www.biopaxwiki.org/cgi-bin/moin.cgi/PSI-MI_Conversion; The Universal Protein Resource (UniProt) (2007) Nucleic Acids Res, 35, pp. D193-D197. , 1669721 17142230 10.1093/nar/gkl929; ChEBI - Chemical Entities of Biological Interest, , http://www.oxfordjournals.org/nar/database/summary/646; Liu, T., Lin, Y., Wen, X., Jorissen, R.N., Gilson, M.K., BindingDB: A web-accessible database of experimentally determined protein-ligand binding affinities (2007) Nucleic Acids Res, 35, pp. D198-D201. , 1751547 17145705 10.1093/nar/gkl999; Cote, R.G., Jones, P., Apweiler, R., Hermjakob, H., The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries (2006) BMC Bioinformatics, 7, p. 97. , 1420335 16507094 10.1186/1471-2105-7-97; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504. , 403769 14597658 10.1101/gr.1239303; Stark, C., Breitkreutz, B.J., Reguly, T., Boucher, L., Breitkreutz, A., Tyers, M., BioGRID: A general repository for interaction datasets (2006) Nucleic Acids Res, 34, pp. D535-D539. , 1347471 16381927 10.1093/nar/gkj109; The International Molecular Exchange Consortium(IMEx), , http://imex.sf.net; Wheeler, D.L., Barrett, T., Benson, D.A., Bryant, S.H., Canese, K., Chetvernin, V., Church, D.M., Federhen, S., Database resources of the National Center for Biotechnology Information (2007) Nucleic Acids Res, 35, pp. D21-D22. , 1781245 17202161 10.1093/nar/gkl1031; Orchard, S., Salwinski, L., Kerrien, S., Montecchi-Palazzi, L., Oesterheld, M., Stümpflen, V., Ceol, A., Woollard, P., The Minimum Information required for reporting a Molecular Interaction Experiment (MIMIx) (2007) Nat Biotechnol, 25, pp. 894-898. , 10.1038/nbt1324 17687370; Hobson, S.D., Rosenblum, E.S., Richards, O.C., Richmond, K., Kirkegaard, K., Schultz, S.C., Oligomeric structures of poliovirus polymerase are important for function (2001) EMBO J, 20, pp. 1153-1163. , 145502 11230138 10.1093/emboj/20.5.1153","Kerrien, S.; European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; email: skerrien@ebi.ac.uk",,,,,,,,17417007,,,10.1186/1741-7007-5-44,17925023,"English","BMC Biol.",Article,Scopus
"Orchard S., Salwinski L., Kerrien S., Montecchi-Palazzi L., Oesterheld M., Stumpflen V., Ceol A., Chatr-Aryamontri A., Armstrong J., Woollard P., Salama J.J., Moore S., Wojcik J., Bader G.D., Vidal M., Cusick M.E., Gerstein M., Gavin A.-C., Superti-Furga G., Greenblatt J., Bader J., Uetz P., Tyers M., Legrain P., Fields S., Mulder N., Gilson M., Niepmann M., Burgoon L., Rivas J.D.L., Prieto C., Perreau V.M., Hogue C., Mewes H.-W., Apweiler R., Xenarios I., Eisenberg D., Cesareni G., Hermjakob H.","The minimum information required for reporting a molecular interaction experiment (MIMIx)",2007,"Nature Biotechnology",25,8,,894,898,,113,"http://www.scopus.com/inward/record.url?eid=2-s2.0-34249107988&partnerID=40&md5=ecf4659493b18bcc46aaeacfcf597ee6","European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; UCLA-US Department of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA, United States; Institute for Bioinformatics, Forschungszentrum für Umwelt und Gesundheit, National Research Center for Environment and Health, Neuherberg, Germany; Department of Molecular Biology, University of Rome Tor Vergata, Rome, Italy; GlaxoSmithkline R and D, Stevenage, United Kingdom; Blueprint Initiative, Samuel Lunenfeld Research Institute, Ont., Canada; National University of Singapore, Clinical Research Centre, Singapore, Singapore; Merck Serono International S.A., Geneva, Switzerland; Banting and Best Department of Medical Research, University of Toronto, Ont., Canada; Center for Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States; Department of Genetics, Harvard Medical School, Boston, MA, United States; Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT, United States; EMBL Heidelberg, Germany; CeMM Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States; Institute of Toxicology and Genetics, Leopoldshafen, Forschungszentrum Karlsruhe, Germany; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; Commissariat à l'Energie Atomique, Institut de Biologie et de Technologie de Saclay, Gif sur Yvette, France; Howard Hughes Medical Institute, Department of Genome Sciences and Medicine, University of Washington, Seattle, WA, United States; Institute for Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; University of Maryland, Biotechnology Institute, Rockville, MD, United States; University of Giessen, Germany; Toxicogenomic Informatics and Solutions, Lansing, MI, United States; Cancer Research Center (Centro de Investigación del Cancer), University of Salamanca, Consejo Superior de Investigaciones Científicas, Salamanca, Spain; Centre for Neuroscience, University of Melbourne, Vic., Australia","Orchard, S., European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Salwinski, L., UCLA-US Department of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA, United States; Kerrien, S., European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Montecchi-Palazzi, L., European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Oesterheld, M., Institute for Bioinformatics, Forschungszentrum für Umwelt und Gesundheit, National Research Center for Environment and Health, Neuherberg, Germany; Stümpflen, V., Institute for Bioinformatics, Forschungszentrum für Umwelt und Gesundheit, National Research Center for Environment and Health, Neuherberg, Germany; Ceol, A., Department of Molecular Biology, University of Rome Tor Vergata, Rome, Italy; Chatr-Aryamontri, A., Department of Molecular Biology, University of Rome Tor Vergata, Rome, Italy; Armstrong, J., GlaxoSmithkline R and D, Stevenage, United Kingdom; Woollard, P., GlaxoSmithkline R and D, Stevenage, United Kingdom; Salama, J.J., Blueprint Initiative, Samuel Lunenfeld Research Institute, Ont., Canada; Moore, S., Blueprint Initiative, Samuel Lunenfeld Research Institute, Ont., Canada, National University of Singapore, Clinical Research Centre, Singapore, Singapore; Wojcik, J., Merck Serono International S.A., Geneva, Switzerland; Bader, G.D., Banting and Best Department of Medical Research, University of Toronto, Ont., Canada; Vidal, M., Center for Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Cusick, M.E., Center for Cancer Systems Biology, Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, United States, Department of Genetics, Harvard Medical School, Boston, MA, United States; Gerstein, M., Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT, United States; Gavin, A.-C., EMBL Heidelberg, Germany; Superti-Furga, G., CeMM Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria; Greenblatt, J., Banting and Best Department of Medical Research, University of Toronto, Ont., Canada; Bader, J., Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States; Uetz, P., Institute of Toxicology and Genetics, Leopoldshafen, Forschungszentrum Karlsruhe, Germany; Tyers, M., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada; Legrain, P., Commissariat à l'Energie Atomique, Institut de Biologie et de Technologie de Saclay, Gif sur Yvette, France; Fields, S., Howard Hughes Medical Institute, Department of Genome Sciences and Medicine, University of Washington, Seattle, WA, United States; Mulder, N., Institute for Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Gilson, M., University of Maryland, Biotechnology Institute, Rockville, MD, United States; Niepmann, M., University of Giessen, Germany; Burgoon, L., Toxicogenomic Informatics and Solutions, Lansing, MI, United States; Rivas, J.D.L., Cancer Research Center (Centro de Investigación del Cancer), University of Salamanca, Consejo Superior de Investigaciones Científicas, Salamanca, Spain; Prieto, C., Cancer Research Center (Centro de Investigación del Cancer), University of Salamanca, Consejo Superior de Investigaciones Científicas, Salamanca, Spain; Perreau, V.M., Centre for Neuroscience, University of Melbourne, Vic., Australia; Hogue, C., Blueprint Initiative, Samuel Lunenfeld Research Institute, Ont., Canada; Mewes, H.-W., Institute for Bioinformatics, Forschungszentrum für Umwelt und Gesundheit, National Research Center for Environment and Health, Neuherberg, Germany; Apweiler, R., European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; Xenarios, I., Merck Serono International S.A., Geneva, Switzerland; Eisenberg, D., UCLA-US Department of Energy, Institute for Genomics and Proteomics, University of California, Los Angeles, CA, United States; Cesareni, G., Department of Molecular Biology, University of Rome Tor Vergata, Rome, Italy; Hermjakob, H., European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom","A wealth of molecular interaction data is available in the literature, ranging from large-scale datasets to a single interaction confirmed by several different techniques. These data are all too often reported either as free text or in tables of variable format, and are often missing key pieces of information essential for a full understanding of the experiment. Here we propose MIMIx, the minimum information required for reporting a molecular interaction experiment. Adherence to these reporting guidelines will result in publications of increased clarity and usefulness to the scientific community and will support the rapid, systematic capture of molecular interaction data in public databases, thereby improving access to valuable interaction data. © 2007 Nature Publishing Group.",,"Data reduction; Information analysis; Systematic errors; Large scale datasets; Molecular interaction data; Systematic capture; Molecular interactions; bioinformatics; data base; mass spectrometry; microarray analysis; molecular interaction; nucleotide sequence; priority journal; proteomics; publication; review; Databases, Protein; Guidelines; Humans; Information Storage and Retrieval; Internationality; Protein Interaction Mapping; Proteomics; Research","GENBANK: NP_005347, P06239, P27986",,,,,"Bader, G.D., Betel, D., Hogue, C.W., BIND: The Biomolecular Interaction Network Database (2003) Nucleic Acids Res, 31, pp. 248-250; Salwinski, L. et al. The Database of Interacting Proteins: 2004 update. Nucleic Acids Res. 32 (Database issue), D449-D451 (2004)Hermjakob, H., The HUPO-PSI's molecular interaction format - a community standard for the representation of protein interaction data (2004) Nat. Biotechnol, 22, pp. 177-183; Orchard, S., Autumn 2005 Workshop of the Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) Geneva, 4-6 September 2005 (2006) Proteomics, 6, pp. 738-741; Shannon, P., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13, pp. 2498-2504; Iragne, F., Nikolski, M., Mathieu, B., Auber, D., Sherman, D., ProViz: Protein interaction visualization and exploration (2005) Bioinformatics, 21, pp. 272-274; Meil, A., Durand, P., Wojcik, J., PIMWalker: Visualising protein interaction networks using the HUPO PSI molecular interaction format (2005) Appl. Bioinformatics, 4, pp. 137-139; Kerrien, S., (2007) Nucleic Acids Res, 35. , IntAct-open source resource for molecular interaction data, Database issue, D561-D565; Chatr-aryamontri, A., (2007) Nucleic Acids Res, 35. , MINT: the Molecular INTeraction database, Database issue, D572-D574; Pagel, P., The MIPS mammalian protein-protein interaction database (2005) Bioinformatics, 21, pp. 832-834; The Universal Protein Resource (UniProt) (2007) Nucleic Acids Res, 35. , The UniProt Consortium, Database issue, D193-D197; Pruitt, K.D., Tatusova, T., Maglott, D.R.N., Reference Sequence project: Update and current status (2003) Nucleic Acids Res, 31, pp. 34-37; Hubbard, T.J., (2007) Nucleic Acids Res, 35. , Ensembl, Database issue, D610-D617; Wheeler, L. et al. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 34 (Database issue), D173-D180 (2006)de Matos, P., (2006) Nucleic Acids Res, , http://www3.oup.co.uk/nar/database/summary/646, ChEBI, Chemical Entities of Biological Interest, Database Summary Paper 646; Taylor, C.F., The minimum information about a proteomics experiment (MIAPE) (2007) Nat. Biotechnol, 25, pp. 887-893; Brazma, A., Minimum information about a microarray experiment (MIAME) - toward standards for microarray data (2001) Nat. Genet, 29, pp. 365-371; Jones, A.R., Pizarro, A., Spellman, P., Miller, M., FuGE: Functional Genomics Experiment object model (2006) OMICS, 10, pp. 179-184. , & FuGE Working Group; Taylor, C.F., Promoting coherent minimum reporting requirements for biological and biomedical investigations: The MIBBI project Nat. Biotechnol, , in the press; Cote, R.G., Jones, P., Apweiler, R., Hermjakob, H., The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries (2006) BMC Bioinformatics [online], 7, p. 97; Croze, E., Receptor for activated C-kinase (RACK-1), a WD motif-containing protein, specifically associates with the human type I IFN receptor (2000) J. Immunol, 165, pp. 5127-5132","Orchard, S.; European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom; email: orchard@ebi.ac.uk",,,,,,,,10870156,,NABIF,10.1038/nbt1324,17687370,"English","Nat. Biotechnol.",Review,Scopus
"Ferro A., Giugno R., Pigola G., Pulvirenti A., Skripin D., Bader G.D., Shasha D.","NetMatch: A Cytoscape plugin for searching biological networks",2007,"Bioinformatics",23,7,,910,912,,28,"http://www.scopus.com/inward/record.url?eid=2-s2.0-34248576314&partnerID=40&md5=230cbd795c667b1d18fe65b51bda90b4","Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; Banting and Best Department of Medical Research, Department of Medical Genetics and Microbiology, University of Toronto, 160 College St, Toronto, ON M5S 3E1, Canada; Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, United States","Ferro, A., Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; Giugno, R., Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; Pigola, G., Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; Pulvirenti, A., Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; Skripin, D., Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; Bader, G.D., Banting and Best Department of Medical Research, Department of Medical Genetics and Microbiology, University of Toronto, 160 College St, Toronto, ON M5S 3E1, Canada; Shasha, D., Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, United States","Summary: NetMatch is a Cytoscape plugin which allows searching biological networks for subcomponents matching a given query. Queries may be approximate in the sense that certain parts of the subgraph-query may be left unspecified. To make the query creation process easy, a drawing tool is provided. Cytoscape is a bioinformatics software platform for the visualization and analysis of biological networks. © The Author 2007. Published by Oxford University Press. All rights reserved.",,"access to information; article; bioinformatics; computer program; gene expression profiling; genetic analysis; information processing; Internet; molecular biology; priority journal; protein interaction; algorithm; biological model; computer graphics; computer interface; computer simulation; data base; information retrieval; methodology; physiology; signal transduction; Algorithms; Computer Graphics; Computer Simulation; Database Management Systems; Information Storage and Retrieval; Models, Biological; Signal Transduction; Software; User-Computer Interface",,,"Cytoscape; NetMatch",,,"Barabási, A.L., Oltvai, Z.N., Network biology: Understanding the cells functional organization (2004) Nature, Genetics Volume, pp. 101-113; Cordella, L., A (sub)graph isomorphism algorithm for matching large graphs (2004) IEEE Trans. on PAMI, 26, pp. 1367-1372; Milo, R., Network motifs: Simple building blocks of complex networks (2002) Science, 298, pp. 824-827; Schreiber, F., Schwobbermeyer, H., Mavisto: A tool for the exploration of network motifs (2003) Bioinformatics, 21, pp. 3572-3574; Shannon, P., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003), 13, pp. 2498-2504. , Genome Research. http://www.cytoscape.orgWernicke, S., Rasche, F., Fanmod: A tool for fast network motif detection (2006) Bioinformatics, 22, pp. 1152-1153; Yip, K.Y., The tyna platform for comparative interactomics: A web tool for managing, comparing and mining multiple networks (2006) Bioinformatics, 22, pp. 2968-2970","Ferro, A.; Dipartimento di Matematica e Informatica, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy; email: ferro@dmi.unict.it",,,,,,,,13674803,,BOINF,10.1093/bioinformatics/btm032,17277332,"English","Bioinformatics",Article,Scopus
"Mathew J.P., Taylor B.S., Bader G.D., Pyarajan S., Antoniotti M., Chinnaiyan A.M., Sander C., Burakoff S.J., Mishra B.","From bytes to bedside: Data integration and computational biology for translational cancer research",2007,"PLoS Computational Biology",3,2,,0153,0163,,19,"http://www.scopus.com/inward/record.url?eid=2-s2.0-33847253388&partnerID=40&md5=dea966d5577e3b2cc06b463f0a901c5b","Dana-Farber Cancer Institute, Boston, MA, United States; Department of Physiology and Biophysics, Weill Medical College, Cornell University, New York, NY, United States; Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ont., Canada; Skirball Institute of Biomolecular Medicine, New York University Cancer Institute, New York, NY, United States; Department of Pathology, New York University School of Medicine, New York, NY, United States; Dipartimento di Informatica Sistemistica e Comunicazione, Università di Milano-Bicocca, Milan, Italy; Departments of Pathology and Urology, Bioinformatics Program, University of Michigan Medical School, Ann Arbor, MI, United States; Courant Institute, New York University, United States; Department of Cell Biology, New York University School of Medicine, New York, NY, United States; Department of Environmental Medicine, New York University School of Medicine, New York, NY, United States; Department of Pathology and Bioinformatics Program, University of Michigan Medical School, Ann Arbor, MI, United States; New York University Bioinformatics Group, Courant Institute, New York University, New York, NY, United States","Mathew, J.P., Dana-Farber Cancer Institute, Boston, MA, United States, Department of Environmental Medicine, New York University School of Medicine, New York, NY, United States; Taylor, B.S., Department of Physiology and Biophysics, Weill Medical College, Cornell University, New York, NY, United States, Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, Department of Pathology and Bioinformatics Program, University of Michigan Medical School, Ann Arbor, MI, United States; Bader, G.D., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ont., Canada; Pyarajan, S., Skirball Institute of Biomolecular Medicine, New York University Cancer Institute, New York, NY, United States, Department of Pathology, New York University School of Medicine, New York, NY, United States; Antoniotti, M., Dipartimento di Informatica Sistemistica e Comunicazione, Università di Milano-Bicocca, Milan, Italy, New York University Bioinformatics Group, Courant Institute, New York University, New York, NY, United States; Chinnaiyan, A.M., Departments of Pathology and Urology, Bioinformatics Program, University of Michigan Medical School, Ann Arbor, MI, United States; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Burakoff, S.J., Skirball Institute of Biomolecular Medicine, New York University Cancer Institute, New York, NY, United States, Department of Pathology, New York University School of Medicine, New York, NY, United States; Mishra, B., Courant Institute, New York University, United States, Department of Cell Biology, New York University School of Medicine, New York, NY, United States","Major advances in genome science and molecular technologies provide new opportunities at the interface between basic biological research and medical practice. The unprecedented completeness, accuracy, and volume of genomic and molecular data necessitate a new kind of computational biology for translational research. Key challenges are standardization of data capture and communication, organization of easily accessible repositories, and algorithms for integrated analysis based on heterogeneous sources of information. Also required are new ways of using complementary clinical and biological data, such as computational methods for predicting disease phenotype from molecular and genetic profiling. New combined experimental and computational methods hold the promise of more accurate diagnosis and prognosis as well as more effective prevention and therapy. © 2007 Mathew et al.",,"antineoplastic agent; bevacizumab; cetuximab; DNA; erlotinib; gefitinib; imatinib; microRNA; rituximab; RNA; small interfering RNA; trastuzumab; tumor protein; antineoplastic activity; breast cancer; cancer diagnosis; cancer prevention; cancer research; cancer therapy; chromosome 13; chronic myeloid leukemia; clinical trial; colorectal cancer; computer assisted tomography; diagnostic accuracy; drug targeting; fluorescence microscopy; gene expression profiling; genetic analysis; genetic variability; genotype environment interaction; head cancer; human; lung non small cell cancer; molecular biology; neck cancer; nuclear magnetic resonance imaging; positron emission tomography; prognosis; protein modification; review; transcription regulation; unspecified side effect; whole body imaging; biology; factual database; medical research; metabolism; methodology; neoplasm; oncology; pathophysiology; research; system analysis; Biomedical Research; Computational Biology; Databases, Factual; Medical Oncology; Neoplasm Proteins; Neoplasms; Research; Research Design; Systems Integration",,"DNA, 9007-49-2; RNA, 63231-63-0; bevacizumab, 216974-75-3; cetuximab, 205923-56-4; erlotinib, 183319-69-9, 183321-74-6; gefitinib, 184475-35-2, 184475-55-6, 184475-56-7; imatinib, 152459-95-5, 220127-57-1; rituximab, 174722-31-7; trastuzumab, 180288-69-1; Neoplasm Proteins","avastin; erbitux; gleevec; herceptin; iressa; rituxan; tarceva",,,"von Mehren, M., Adams, G.P., Weiner, L.M., Monoclonal antibody therapy for cancer (2003) Annu Rev Med, 54, pp. 343-369; (2004) US Federal Drug Administration, Challenge and opportunity on the critical path to new medical products, , http://www. fda.gov/oc/initiatives/criticalpath/whitepaper.pdf, FDA , Available:, Accessed 25 December; Fabian, M.A., Biggs III, W.H., Treiber, D.K., Atteridge, C.E., Azimioara, M.D., A small molecule-kinase interaction map for clinical kinase inhibitors (2005) Nat Biotechnol, 23, pp. 329-336; McNeil, N., Ried, T., Novel molecular cytogenetic techniques for identifying complex chromosomal rearrangements: Technology and applications in molecular medicine (2000) Expert Rev Mol Med 2000, pp. 1-14; Baldwin, C., Garnis, C., Zhang, L., Rosin, M.P., Lam, W.L., Multiple microalterations detected at high frequency in oral cancer (2005) Cancer Res, 65, pp. 7561-7567; Rauch, A., Ruschendorf, F., Huang, J., Trautmann, U., Becker, C., Molecular karyotyping using an SNP array for genomewide genotyping (2004) J Med Genet, 41, pp. 916-922; The International HapMap Project (2003) Nature, 426, pp. 789-796. , Consortium TIH; Robertson, K.D., DNA methylation and human disease (2005) Nat Rev Genet, 6, pp. 597-610; Schena, M., Shalon, D., Davis, R.W., Brown, P.O., Quantitative monitoring of gene expression patterns with a complementary DNA microarray (1995) Science, 270, pp. 467-470; Lockhart, D.J., Dong, H., Byrne, M.C., Follettie, M.T., Gallo, M.V., Expression monitoring by hybridization to high-density oligonucleotide arrays (1996) Nat Biotechnol, 14, pp. 1675-1680; Brenner, S., Johnson, M., Bridgham, J., Golda, G., Lloyd, D.H., Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays (2000) Nat Biotechnol, 18, pp. 630-634; Golub, T.R., Slonim, D.K., Tamayo, P., Huard, C., Gaasenbeek, M., Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring (1999) Science, 286, pp. 531-537; Dhanasekaran, S.M., Barrette, T.R., Ghosh, D., Shah, R., Varambally, S., Delineation of prognostic biomarkers in prostate cancer (2001) Nature, 412, pp. 822-826; Blais, A., Dynlacht, B.D., Constructing transcriptional regulatory networks (2005) Genes Dev, 19, pp. 1499-1511; Ross, D.T., Scherf, U., Eisen, M.B., Perou, C.M., Rees, C., Systematic variation in gene expression patterns in human cancer cell lines (2000) Nat Genet, 24, pp. 227-235; Scherf, U., Ross, D.T., Waltham, M., Smith, L.H., Lee, J.K., A gene expression database for the molecular pharmacology of cancer (2000) Nat Genet, 24, pp. 236-244; Creighton, C.J., Bromberg-White, J.L., Misek, D.E., Monsma, D.J., Brichory, F., Analysis of tumor-host interactions by gene expression profiling of lung adenocarcinoma xenografts identifies genes involved in tumor formation (2005) Mol Cancer Res, 3, pp. 119-129; Ficarro, S.B., McCleland, M.L., Stukenberg, P.T., Burke, D.J., Ross, M.M., Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae (2002) Nat Biotechnol, 20, pp. 301-305; Mann, M., Ong, S.E., Gronborg, M., Steen, H., Jensen, O.N., Analysis of protein phosphorylation using mass spectrometry: Deciphering the phosphoproteome (2002) Trends Biotechnol, 20, pp. 261-268; Wells L, Vosseller K, Cole RN, Cronshaw JM, Matunis MJ, et al. 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Hermjakob, H., Montecchi-Palazzi, L., Bader, G., Wojcik, J., Salwinski, L., The HUPO PSI's molecular interaction format - A community standard for the representation of protein interaction data (2004) Nat Biotechnol, 22, pp. 177-183","Mathew, J.P.; Dana-Farber Cancer Institute, Boston, MA, United States; email: Jomol_Mathew@dfci.harvard.edu",,,,,,,,1553734X,,,10.1371/journal.pcbi.0030012,17319736,"English","PLoS Comput. Biol.",Review,Scopus
"Cerami E.G., Bader G.D., Gross B.E., Sander C.","cPath: Open source software for collecting, storing, and querying biological pathways",2006,"BMC Bioinformatics",7,, 497,,,,53,"http://www.scopus.com/inward/record.url?eid=2-s2.0-33751435209&partnerID=40&md5=94f6c8e36c8cbfa869a352740aca9fc1","Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St., Toronto, ON M5S 3E1, Canada","Cerami, E.G., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States; Bader, G.D., Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St., Toronto, ON M5S 3E1, Canada; Gross, B.E., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States","Background: Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required. Results: We have developed cPath, an open source database and web application for collecting, storing, and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and export pathway data via a web service to third party software, such as Cytoscape, for visualization and analysis. cPath is software only, and does not include new pathway information. Key features include: a built-in identifier mapping service for linking identical interactors and linking to external resources; built-in support for PSI-MI and BioPAX standard pathway exchange formats; a web service interface for searching and retrieving pathway data sets; and thorough documentation. The cPath software is freely available under the LGPL open source license for academic and commercial use. Conclusion: cPath is a robust, scalable, modular, professional-grade software platform for collecting, storing, and querying biological pathways. It can serve as the core data handling component in information systems for pathway visualization, analysis and modeling. © 2006 Cerami et al; licensee BioMed Central Ltd.",,"article; bioinformatics; computer analysis; computer interface; computer program; data base; data collection method; information processing; information system; Internet; systems biology",,,,,,"Ideker, T., Galitski, T., Hood, L., A new approach to decoding life: Systems biology (2001) Annu Rev Genomics Hum Genet, 2, pp. 343-372; Schaefer, C.F., Pathway databases (2004) Ann N Y Acad Sci, 1020, pp. 77-91; Kitano, H., Systems biology: A brief overview (2002) Science, 295 (5560), pp. 1662-1664; Ideker, T., Thorsson, V., Ranish, J.A., Christmas, R., Buhler, J., Eng, J.K., Bumgamer, R., Hood, L., Integrated genomic and proteomic analyses of a systematically perturbed metabolic network (2001) Science, 292 (5518), pp. 929-934; Hanahan, D., Weinberg, R.A., The hallmarks of cancer (2000) Cell, 100 (1), pp. 57-70; Hahn, W.C., Weinberg, R.A., Modelling the molecular circuitry of cancer (2002) Nat Rev Cancer, 2 (5), pp. 331-341; 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Lloyd, C.M., Halstead, M.D., Nielsen, P.F., CellML: Its future, present and past (2004) Prog Biophys Mol Biol, 85 (2-3), pp. 433-450; http//www.biopax.org/, BioPAX: Biological Pathways ExchangeBader, G.D., Cary, M.P., Sander, C., Pathguide: A pathway resource list (2006) Nucleic Acids Res, 34, pp. D504-D506. , (Database issue); Aragues, R., Jaeggi, D., Oliva, B., PIANA: Protein interactions and network analysis (2006) Bioinformatics, 22 (8), pp. 1015-1017; Kohler, J., Baumbach, J., Taubert, J., Specht, M., Skusa, A., Ruegg, A., Rawlings, C., Philippi, S., Graph-based analysis and visualization of experimental results with ONDEX (2006) Bioinformatics, 22 (11), pp. 1383-1390; Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Ideker, T., Cytoscape: A software environment for integrated models of biomolecular interaction networks (2003) Genome Res, 13 (11), pp. 2498-2504; Zdobnov, E.M., Lopez, R., Apweiler, R., Etzold, T., The EBI SRS server - Recent developments (2002) Bioinformatics, 18 (2), pp. 368-373; 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Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States; email: cpath-bmc@cbio.mskcc.org",,,,,,,,14712105,,BBMIC,10.1186/1471-2105-7-497,,"English","BMC Bioinform.",Article,Scopus
"Bader G.D., Cary M.P., Sander C.","Pathguide: a pathway resource list.",2006,"Nucleic acids research.",34,Database issue,,D504,506,,121,"http://www.scopus.com/inward/record.url?eid=2-s2.0-33644873677&partnerID=40&md5=876a29f8533304dec87ca4bbd6dc13f1","Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10021, USA.","Bader, G.D., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10021, USA.; Cary, M.P., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10021, USA.; Sander, C., Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, NY 10021, USA.","Pathguide: the Pathway Resource List (http://pathguide.org) is a meta-database that provides an overview of more than 190 web-accessible biological pathway and network databases. These include databases on metabolic pathways, signaling pathways, transcription factor targets, gene regulatory networks, genetic interactions, protein-compound interactions, and protein-protein interactions. The listed databases are maintained by diverse groups in different locations and the information in them is derived either from the scientific literature or from systematic experiments. Pathguide is useful as a starting point for biological pathway analysis and for content aggregation in integrated biological information systems.",,"protein; transcription factor; article; chemistry; computer interface; gene expression regulation; genetic database; Internet; metabolism; signal transduction; standard; system analysis; Databases, Genetic; Gene Expression Regulation; Internet; Metabolism; Proteins; Signal Transduction; Systems Integration; Transcription Factors; User-Computer Interface",,"protein, 67254-75-5; Proteins; Transcription Factors",,,,,"Bader, G.D.",,,,,,,,13624962,,,,16381921,"English","Nucleic Acids Res",Article,Scopus
"Cary M.P., Bader G.D., Sander C.","Pathway information for systems biology",2005,"FEBS Letters",579,8,,1815,1820,,60,"http://www.scopus.com/inward/record.url?eid=2-s2.0-14844332708&partnerID=40&md5=7e5050af75333cc3aadf2a6c5577cf92","Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States","Cary, M.P., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; Bader, G.D., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; Sander, C., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States","Pathway information is vital for successful quantitative modeling of biological systems. The almost 170 online pathway databases vary widely in coverage and representation of biological processes, making their use extremely difficult. Future pathway information systems for querying, visualization and analysis must support standard exchange formats to successfully integrate data on a large scale. Such integrated systems will greatly facilitate the constructive cycle of computational model building and experimental verification that lies at the heart of systems biology. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.","Information system; Ontology; Pathway data integration; Pathway database; Standard exchange format","complementary DNA; bioprocess; data base; enzyme metabolism; gene construct; gene control; human; mathematical computing; mathematical model; nonhuman; online system; priority journal; protein protein interaction; short survey; signal transduction; standard; Animals; Computational Biology; Databases, Factual; Humans; Models, Biological; Protein Binding; Signal Transduction",,,,,,"Ideker, T., Galitski, T., Hood, L., A new approach to decoding life: Systems biology (2001) Annu. Rev. Genomics Hum. 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Stat., 14 (3), pp. 701-721; Stein, L.D., Integrating biological databases (2003) Nat. Rev. Genet., 4 (5), pp. 337-345; Lloyd, C.M., Halstead, M.D., Nielsen, P.F., CellML: Its future, present and past (2004) Prog. Biophys. Mol. Biol., 85 (2-3), pp. 433-450; Hucka, M., The systems biology markup language (SBML): A medium for representation and exchange of biochemical network models (2003) Bioinformatics, 19 (4), pp. 524-531; Keseler, I.M., EcoCyc: A comprehensive database resource for Escherichia coli (2005) Nucleic Acids Res., 33 (DATABASE ISSUE), pp. 334-D337; Aladjem, M.I., Molecular interaction maps - A diagrammatic graphical language for bioregulatory networks (2004) Sci. STKE, 2004 (222), p. 8","Cary, M.P.; Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States",,,,,,,,00145793,,FEBLA,10.1016/j.febslet.2005.02.005,15763557,"English","FEBS Lett.",Short Survey,Scopus
"Tong A.H.Y., Lesage G., Bader G.D., Ding H., Xu H., Xin X., Young J., Berriz G.F., Brost R.L., Chang M., Chen Y., Cheng X., Chua G., Friesen H., Goldberg D.S., Haynes J., Humphries C., He G., Hussein S., Ke L., Krogan N., Li Z., Levinson J.N., Lu H., Menard P., Munyana C., Parsons A.B., Ryan O., Tonikian R., Roberts T., Sdicu A.-M., Shapiro J., Sheikh B., Suter B., Wong S.L., Zhang L.V., Zhu H., Burd C.G., Munro S., Sander C., Rine J., Greenblatt J., Peter M., Bretscher A., Bell G., Roth F.P., Brown G.W., Andrews B., Bussey H., Boone C.","Global Mapping of the Yeast Genetic Interaction Network",2004,"Science",303,5659,,808,813,,1048,"http://www.scopus.com/inward/record.url?eid=2-s2.0-10744230485&partnerID=40&md5=f5f3c0a7e8b6024fb864e93f78690ee2","Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Dept. of Molec. Biology and Genetics, 351 Biotechnology Building, Cornell University, Ithaca, NY 14853, United States; Harvard Medical School, Dept. Biol. Chem./Molec. Pharmacol., 250 Longwood Avenue, Boston, MA 02115, United States; Dept. of Molecular and Cell Biology, University of California, 16 Barker Hall, Berkeley, CA 94720-3202, United States; Univ. of Pennsylvania Sch. of Med., Dept. of Cell and Devmtl. Biology, BRB 2/3, 421 Curie Boulevard, Philadelphia, PA 19104-6058, United States; MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, United Kingdom; Institute of Biochemistry, HPM G8.0, ETH Hoenggerberg, 8093, Zurich, Switzerland","Tong, A.H.Y., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Lesage, G., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Bader, G.D., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; Ding, H., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Xu, H., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Xin, X., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Young, J., Dept. of Molec. Biology and Genetics, 351 Biotechnology Building, Cornell University, Ithaca, NY 14853, United States; Berriz, G.F., Harvard Medical School, Dept. Biol. Chem./Molec. Pharmacol., 250 Longwood Avenue, Boston, MA 02115, United States; Brost, R.L., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Chang, M., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Chen, Y., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Cheng, X., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Chua, G., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Friesen, H., Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Goldberg, D.S., Harvard Medical School, Dept. Biol. Chem./Molec. Pharmacol., 250 Longwood Avenue, Boston, MA 02115, United States; Haynes, J., Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Humphries, C., Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; He, G., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Hussein, S., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Ke, L., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Krogan, N., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Li, Z., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Levinson, J.N., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Lu, H., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Ménard, P., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Munyana, C., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Parsons, A.B., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Ryan, O., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Tonikian, R., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Roberts, T., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Sdicu, A.-M., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Shapiro, J., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Sheikh, B., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Suter, B., Dept. of Molecular and Cell Biology, University of California, 16 Barker Hall, Berkeley, CA 94720-3202, United States; Wong, S.L., Harvard Medical School, Dept. Biol. Chem./Molec. Pharmacol., 250 Longwood Avenue, Boston, MA 02115, United States; Zhang, L.V., Harvard Medical School, Dept. Biol. Chem./Molec. Pharmacol., 250 Longwood Avenue, Boston, MA 02115, United States; Zhu, H., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada; Burd, C.G., Univ. of Pennsylvania Sch. of Med., Dept. of Cell and Devmtl. Biology, BRB 2/3, 421 Curie Boulevard, Philadelphia, PA 19104-6058, United States; Munro, S., MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, United Kingdom; Sander, C., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; Rine, J., Dept. of Molecular and Cell Biology, University of California, 16 Barker Hall, Berkeley, CA 94720-3202, United States; Greenblatt, J., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Peter, M., Institute of Biochemistry, HPM G8.0, ETH Hoenggerberg, 8093, Zurich, Switzerland; Bretscher, A., Dept. of Molec. Biology and Genetics, 351 Biotechnology Building, Cornell University, Ithaca, NY 14853, United States; Bell, G., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Roth, F.P., Harvard Medical School, Dept. Biol. Chem./Molec. Pharmacol., 250 Longwood Avenue, Boston, MA 02115, United States; Brown, G.W., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Andrews, B., Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; Bussey, H., Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montreal, Que. H3A 1B1, Canada; Boone, C., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5G 1L6, Canada, Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada","A genetic interaction network containing ∼1000 genes and ∼4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ∼4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.",,"Defects; Mutagenesis; Yeast; Genetic interaction network; Mutants; Genes; yeast; article; fungal gene; gene cluster; gene function; gene mapping; molecular interaction; nonhuman; prediction; priority journal; Saccharomyces cerevisiae; Amino Acid Sequence; Computational Biology; Cystic Fibrosis; Gene Deletion; Genes, Essential; Genes, Fungal; Genetic Diseases, Inborn; Genotype; Humans; Molecular Sequence Data; Multifactorial Inheritance; Mutation; Phenotype; Polymorphism, Genetic; Retinitis Pigmentosa; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae",,"Saccharomyces cerevisiae Proteins",,,,"Dolinski, K., Saccharomyces Genome Database (5GD), , www.yeastgenome.org; Giaever, G., (2002) Nature, 418, p. 387; Tong, A.H., (2001) Science, 294, p. 2364; Hartman, J.L., Garvik, B., Hartwell, L., (2001) Science, 291, p. 1001; notenoteAshburner, M., (2000) Nature Genet., 25, p. 25; noteMayer, M.L., Gygi, S.P., Aebersold, R., Hieter, P., (2001) Mol. 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Genet., 3, p. 779; Nadeau, J.H., (2001) Nature Rev. Genet., 2, p. 165; Kajiwara, K., Berson, E.L., Dryja, T.P., (1994) Science, 264, p. 1604; Berriz, G.F., King, O.D., Bryant, B., Sander, C., Roth, F.P., Bioinformatics, , in press; note","Andrews, B.; Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S 1A8, Canada; email: brenda.andrews@utoronto.ca",,,,,,,,00368075,,SCIEA,10.1126/science.1091317,14764870,"English","Science",Article,Scopus
"Andrews B.J., Bader G.D., Boone C.","Playing tag with the yeast proteome",2003,"Nature Biotechnology",21,11,,1297,1299,,5,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0242290928&partnerID=40&md5=38b82f4e6cce198ef9c0a9813b10eee7","Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S IA8, Canada; Dept. of Med. Genet. and Microbiol., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5S IA8, Canada; Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Ave., New York, NY 10021, United States","Andrews, B.J., Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S IA8, Canada; Bader, G.D., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Ave., New York, NY 10021, United States; Boone, C., Dept. of Med. Genet. and Microbiol., Banting and Best Dept. of Med. Res., University of Toronto, Toronto, Ont. M5S IA8, Canada",[No abstract available],,"proteome; fungal strain; gene sequence; genome; nonhuman; polymerase chain reaction; priority journal; protein expression; protein function; proteomics; short survey; Western blotting; yeast; Epitopes; Expressed Sequence Tags; Gene Expression Profiling; Genome, Fungal; Open Reading Frames; Proteome; Proteomics; Recombinant Fusion Proteins; RNA, Fungal; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins",,"Epitopes; Proteome; Recombinant Fusion Proteins; RNA, Fungal; Saccharomyces cerevisiae Proteins",,,,"Ghaemmaghami, S., (2003) Nature, 425, pp. 737-741; Huh, W.-K., (2003) Nature, 425, pp. 686-691; Phizicky, E.M., Bastiaens, P.I.H., Zhu, H., Snyder, M., Fields, S., (2003) Nature, 422, pp. 208-215; Washburn, M.P., Wolters, D., Yates, J.R., (2001) Nat. Biotechnol., 19, pp. 242-247; Kumar, A., (2002) Genes Dev., 16, pp. 707-719; Ihmels, J., (2002) Nat. Genet., 31, pp. 370-377; Dimster-Denk, D., (1999) J. Lipid Res., 40, pp. 850-860; Tong, A.H.Y., (2001) Science, 294, pp. 2364-2368","Andrews, B.J.; Dept. of Med. Genet. and Microbiol., University of Toronto, Toronto, Ont. M5S IA8, Canada; email: brenda.andrews@utoronto.ca",,,,,,,,10870156,,NABIF,10.1038/nbt1103-1297,14595360,"English","Nat. Biotechnol.",Short Survey,Scopus
"Bader G.D., Heilbut A., Andrews B., Tyers M., Hughes T., Boone C.","Functional genomics and proteomics: Charting a multidimensional map of the yeast cell",2003,"Trends in Cell Biology",13,7,,344,356,,70,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0037756723&partnerID=40&md5=ff8c1ceae48fc5b6b6bcca7c777aac9c","Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Dept. of Med. Genet./Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Ont. M5S 1A8, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University Avenue, Toronto, Ont. M5G 1X5, Canada; Banting/Best Dept. of Med. Research, University of Toronto, 112 College St., Toronto, Ont. M5G 1L6, Canada","Bader, G.D., Computational Biology Center, Mem. Sloan-Kettering Cancer Center, Box 460, 1275 York Avenue, New York, NY 10021, United States; Heilbut, A., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Andrews, B., Dept. of Med. Genet./Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Ont. M5S 1A8, Canada; Tyers, M., Dept. of Med. Genet./Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University Avenue, Toronto, Ont. M5G 1X5, Canada; Hughes, T., Dept. of Med. Genet./Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Ont. M5S 1A8, Canada, Banting/Best Dept. of Med. Research, University of Toronto, 112 College St., Toronto, Ont. M5G 1L6, Canada; Boone, C., Dept. of Med. Genet./Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Ont. M5S 1A8, Canada, Banting/Best Dept. of Med. Research, University of Toronto, 112 College St., Toronto, Ont. M5G 1L6, Canada","The challenge of large-scale functional genomics projects is to build a comprehensive map of the cell including genome sequence and gene expression data, information on protein localization, structure, function and expression, post-translational modifications, molecular and genetic interactions and phenotypic descriptions. Some of this broad set of functional genomics data has been already assembled for the budding yeast. Even though molecular cartography of the yeast cell is still far from comprehensive, functional genomics has begun to forge connections between disparate cellular events and to foster numerous hypotheses. Here we review several different genomics and proteomics technologies and describe bioinformatics methods for exploring these data to make new discoveries.",,"RNA; analytic method; bioinformatics; biotechnology; cross linking; crystal structure; cytology; data analysis; DNA microarray; fungal genetics; gene deletion; gene expression; gene expression profiling; gene interaction; gene mapping; gene mutation; gene sequence; gene structure; gene technology; genetic code; genetic database; genetic transcription; genome analysis; genomics; molecular interaction; phenotype; polymerase chain reaction; priority journal; protein analysis; protein DNA interaction; protein expression; protein function; protein localization; protein processing; protein protein interaction; protein structure; proteomics; quantitative analysis; review; sequence analysis; structure analysis; transcription regulation; validation process; yeast cell; Chromosome Mapping; Computational Biology; Gene Expression Regulation, Fungal; Genomics; Nuclear Proteins; Proteomics; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Fungi; Myxogastria; Saccharomycetales",,"RNA, 63231-63-0; Nuclear Proteins; Saccharomyces cerevisiae Proteins",,,,"Fields, S., Proteomics. 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M5S 1A8, Canada; email: charlie.boone@utoronto.ca",,,,,,,,09628924,,TCBIE,10.1016/S0962-8924(03)00127-2,12837605,"English","Trends Cell Biol.",Review,Scopus
"Donaldson I., Martin J., de Bruijn B., Wolting C., Lay V., Tuekam B., Zhang S., Baskin B., Bader G.D., Michalickova K., Pawson T., Hogue C.W.V.","PreBIND and textomy - Mining the biomedical literature for protein-protein interactions using a support vector machine",2003,"BMC Bioinformatics",4,, 11,,,13,81,"http://www.scopus.com/inward/record.url?eid=2-s2.0-2942549190&partnerID=40&md5=3fa219bc0529acb3c926aff9480c1519","Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada; Institute for Information Technology, National Research Council of Canada, Ottawa, Ont. K1A 0R6, Canada; MDS Proteomics Inc., Toronto, Ont. M9W 7H4, Canada; Dept. of Biochemistry, University of Toronto, Toronto, Ont., Canada; Computational Biology Center, Memorial Sloan-Kettering Cancer, 1275 York Avenue, New York, NY 10021, United States; Dept. of Molecular/Medical Genetics, University of Toronto, Toronto, Ont., Canada","Donaldson, I., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada; Martin, J., Institute for Information Technology, National Research Council of Canada, Ottawa, Ont. K1A 0R6, Canada; de Bruijn, B., Institute for Information Technology, National Research Council of Canada, Ottawa, Ont. K1A 0R6, Canada; Wolting, C., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada; Lay, V., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada; Tuekam, B., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada; Zhang, S., MDS Proteomics Inc., Toronto, Ont. M9W 7H4, Canada; Baskin, B., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada; Bader, G.D., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada, Dept. of Biochemistry, University of Toronto, Toronto, Ont., Canada, Computational Biology Center, Memorial Sloan-Kettering Cancer, 1275 York Avenue, New York, NY 10021, United States; Michalickova, K., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada, Dept. of Biochemistry, University of Toronto, Toronto, Ont., Canada; Pawson, T., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada, Dept. of Molecular/Medical Genetics, University of Toronto, Toronto, Ont., Canada; Hogue, C.W.V., Samuel Lunenfeld Research Institute, Toronto, Ont. M4G 1X5, Canada, Dept. of Biochemistry, University of Toronto, Toronto, Ont., Canada","Background: The majority of experimentally verified molecular interaction and biological pathway data are present in the unstructured text of biomedical journal articles where they are inaccessible to computational methods. The Biomolecular interaction network database (BIND) seeks to capture these data in a machine-readable format. We hypothesized that the formidable task-size of backfilling the database could be reduced by using Support Vector Machine technology to first locate interaction information in the literature. We present an information extraction system that was designed to locate protein-protein interaction data in the literature and present these data to curators and the public for review and entry into BIND. Results: Cross-validation estimated the support vector machine's test-set precision, accuracy and recall for classifying abstracts describing interaction information was 92%, 90% and 92% respectively. We estimated that the system would be able to recall up to 60% of all non-high throughput interactions present in another yeast-protein interaction database. Finally, this system was applied to a real-world curation problem and its use was found to reduce the task duration by 70% thus saving 176 days. Conclusions: Machine learning methods are useful as tools to direct interaction and pathway database back-filling; however, this potential can only be realized if these techniques are coupled with human review and entry into a factual database such as BIND. The PreBIND system described here is available to the public at http://bind.ca. Current capabilities allow searching for human, mouse and yeast protein-interaction information. © 2003 Donaldson et al; licensee BioMed Central Ltd.",,"amino acid sequence; computer; computer program; controlled study; factual database; gene locus; information system; mathematical computing; molecular interaction; nonhuman; protein protein interaction; review; Saccharomyces cerevisiae; sequence database; validation process; yeast",,,"Biomolecular Interaction Network Database; CodeBase, Sequiter Software; Linux; PreBIND; Solaris; Windows","Sequiter Software",,"Bader, G.D., Hogue, C.W., BIND - A data specification for storing and describing biomolecular interactions, molecular complexes and pathways (2000) Bioinformatics, 16, pp. 465-477; Bader, G.D., Donaldson, I., Wolting, C., Ouellette, B.F., Pawson, T., Hogue, C.W., BIND - The Biomolecular Interaction Network Database (2001) Nucleic Acids Res., 29, pp. 242-245; Sekimizu, T., Park, H.S., Tsujii, J., Identifying the Interaction between Genes and Gene Products Based on Frequently Seen Verbs in Medline Abstracts (1998) Genome Inform. 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Biotechnol., 20, pp. 991-997; Ostell, J.M., Wheelan, S.J., Kans, J.A., The NCBI data model (2001) Methods Biochem. Anal., 43, pp. 19-43; McCallum, A.K., Bow: A toolkit for statistical language modeling, text retrieval, classification and clustering (1996), http://www.cs.cmu.edu/~mccallum/bow","Hogue, C.W.V.; Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; email: hogue@mshri.on.ca",,,,,,,,14712105,,BBMIC,10.1186/1471-2105-4-11,,"English","BMC Bioinform.",Article,Scopus
"Donaldson I., Martin J., de Bruijn B., Wolting C., Lay V., Tuekam B., Zhang S., Baskin B., Bader G.D., Michalickova K., Pawson T., Hogue C.W.","PreBIND and Textomy--mining the biomedical literature for protein-protein interactions using a support vector machine.",2003,"BMC bioinformatics [electronic resource]",4,1,,11,,,80,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0642371101&partnerID=40&md5=6f25a104665f09588bcdcf4e6e80e0e0","Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.","Donaldson, I., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Martin, J., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; de Bruijn, B., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Wolting, C., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Lay, V., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Tuekam, B., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Zhang, S., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Baskin, B., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Bader, G.D., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Michalickova, K., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Pawson, T., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.; Hogue, C.W., Samuel Lunenfeld Research Institute, Toronto, M5G 1X5, Canada.","BACKGROUND: The majority of experimentally verified molecular interaction and biological pathway data are present in the unstructured text of biomedical journal articles where they are inaccessible to computational methods. The Biomolecular interaction network database (BIND) seeks to capture these data in a machine-readable format. We hypothesized that the formidable task-size of backfilling the database could be reduced by using Support Vector Machine technology to first locate interaction information in the literature. We present an information extraction system that was designed to locate protein-protein interaction data in the literature and present these data to curators and the public for review and entry into BIND. RESULTS: Cross-validation estimated the support vector machine's test-set precision, accuracy and recall for classifying abstracts describing interaction information was 92%, 90% and 92% respectively. We estimated that the system would be able to recall up to 60% of all non-high throughput interactions present in another yeast-protein interaction database. Finally, this system was applied to a real-world curation problem and its use was found to reduce the task duration by 70% thus saving 176 days. CONCLUSIONS: Machine learning methods are useful as tools to direct interaction and pathway database back-filling; however, this potential can only be realized if these techniques are coupled with human review and entry into a factual database such as BIND. The PreBIND system described here is available to the public at http://bind.ca. Current capabilities allow searching for human, mouse and yeast protein-interaction information.",,"Saccharomyces cerevisiae protein; algorithm; article; artificial intelligence; biology; chemistry; classification; comparative study; evaluation; factual database; genetics; genome; information retrieval; MEDLINE; methodology; protein analysis; protein database; Saccharomyces cerevisiae; statistics; validation study; Algorithms; Artificial Intelligence; Computational Biology; Databases, Factual; Databases, Protein; Genome, Fungal; Information Storage and Retrieval; Protein Interaction Mapping; PubMed; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins",,"Saccharomyces cerevisiae Proteins",,,,,"Donaldson, I.email: ian.donaldson@utoronto.ca",,,,,,,,14712105,,,,12689350,"English","BMC Bioinformatics",Article,Scopus
"Sidhu S.S., Bader G.D., Boone C.","Functional genomics of intracellular peptide recognition domains with combinatorial biology methods",2003,"Current Opinion in Chemical Biology",7,1,,97,102,,15,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0037305940&partnerID=40&md5=0f40c0987dce8b32f5a7bcd7de4b509b","Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ont. M5S 1A8, Canada; Computational Biology Center, Mem. Sloan-Kattering Cancer Center, 1275 York Avenue, New York, NY 10021, United States","Sidhu, S.S., Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States; Bader, G.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ont. M5S 1A8, Canada, Computational Biology Center, Mem. Sloan-Kattering Cancer Center, 1275 York Avenue, New York, NY 10021, United States; Boone, C.","Phage-displayed peptide libraries have been used to identify specific ligands for peptide-binding domains that mediate intracellular protein-protein interactions. These studies have provided significant insights into the specificities of particular domains. For PDZ domains that recognize C-terminal sequences, the information has proven useful in identifying natural binding partners from genomic databases. For SH3 domains that recognize internal proline-rich motifs, the results of database searches with phage-derived ligands have been compared with the results of yeast-two-hybrid experiments to produce overlap networks that reliably predict natural protein-protein interactions. In addition, libraries of phage-displayed PDZ and SH3 domains have been used to identify the residues responsible for ligand recognition, and also to engineer domains with altered specificities.",,"peptide; protein; bacteriophage; binding affinity; biology; carboxy terminal sequence; genomics; protein domain; protein motif; protein protein interaction; review; yeast; Databases, Protein; Genomics; Peptide Library; Peptides; Protein Binding; Protein Structure, Tertiary; Structural Homology, Protein; Two-Hybrid System Techniques",,"protein, 67254-75-5; Peptide Library; Peptides",,,,"Pawson, T., Protein modules and signalling networks (1995) Nature, 373, pp. 573-580; Pawson, T., Scott, J.D., Signaling through scaffold, anchoring and adapter proteis (1997) Science, 278, pp. 2075-2080; Sudol, M., From Src homology domains to other signaling modules: Proposal of the 'protein recognition code' (1998) Oncogene, 17, pp. 1469-1474; Aasland, R., Abrams, C., Ampe, C., Ball, L.J., Bedford, M.T., Cesareni, G., Gimona, M., Lehto, V.P., Normalization of nomenclature for peptide motifs as ligands of modular protein domains (2002) FEBS Lett., 513, pp. 141-144. , The authors propose a general nomenclature for describing residue preferences in peptide motifs recognized by peptide-binding domains. Universal acceptance of the code would greatly reduce the current confusion in the description of binding motifs; Kay, B.K., Kasanov, J., Knight, S., Kurakin, A., Convergent evolution with combinatorial libraries (2000) FEBS Lett., 480, pp. 55-62; Sidhu, S.S., Phage display in pharmaceutical biotechnology (2000) Curr. Opin. Biotechnol., 11, pp. 610-616; Sidhu, S.S., Lowman, H.B., Cunningham, B.C., Wells, J.A., Phage display for selection of novel binding peptides (2000) Meth. Enzymol., 328, pp. 333-363; Craven, S.E., Bredt, D.S., PDZ proteins organize synaptic signaling pathways (1998) Cell, 93, pp. 495-498; Fanning, A.S., Anderson, J.M., Protein modules as organizers of membrane structure (1999) Curr. Opin. Cell. Biol., 11, pp. 432-439; Schultz, J., Copley, R.R., Doerks, T., Ponting, C.P., Bork, P., SMART: A web-based tool for the study of genetically mobile domains (2000) Nucl. Acid Res., 28, pp. 231-234; Doyle, D.A., Lee, A., Lewis, J., Kim, E., Sheng, M., MacKinnon, R., Crystal structures of a complexed and peptide-free membrane protein-binding domain: Molecular basis of peptide recognition by PDZ (1996) Cell, 85, pp. 1067-1076; Karthikeyan, S., Leung, T., Ladias, J.A.A., Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the β2 adrenergic and platelet-derived growth factor receptors (2002) J. Biol. Chem., 277, pp. 18973-18978; Harrison, S.C., Peptide-surface association: The case of PDZ and PTB domains (1996) Cell, 86, pp. 341-343; Harris, B.Z., Lim, W.A., Mechanism and role of PDZ domains in signaling complex assembly (2001) J. Cell. Sci., 114, pp. 3219-3231; Hung, A.Y., Sheng, M., PDZ domains: Structural modules for protein complex assembly (2002) J. Biol. Chem., 277, pp. 5699-5702; Songyang, Z., Fanning, A.S., Fu, C., Xu, J., Marfatia, S.M., Chishti, A.H., Crompton, A., Cantley, L.C., Recognition of unique carboxyl-terminal motifs by distinct PDZ domains (1997) Science, 275, pp. 73-77; Stricker, N.L., Christopherson, K.S., Yi, B.A., Schatz, P.J., Raab, R.W., Dawes, G., Bassett D.E., Jr., Li, M., PDZ domain of neuronal nitric oxide synthase recognizes novel C-terminal peptide sequences (1997) Nature Biotechnol., 15, pp. 336-342; Fuh, G., Pisabarro, M.T., Li, Y., Quan, C., Lasky, L.A., Sidhu, S.S., Analysis of PDZ domain-ligand interactions using carboxyl-terminal phage display (2000) J. Biol. Chem., 275, pp. 21486-21491; Laura, R.P., Witt, A.S., Held, H.A., Gerstner, R., Deshayes, K., Koehler, M.F., Kosik, K.S., Lasky, L.A., The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF (2002) J. Biol. Chem., 277, pp. 12906-12914. , This paper demonstrates that phage-derived peptide sequences can be used to identify natural binding partners for PDZ domains. The work also emphasizes the need for several independent methods to definitively validate a biologically relevant protein-protein interaction. Using database mining with phage-derived consensus sequences, followed by affinity measurements with synthetic peptides and cell biology experiments, the p120-related catenins were shown to be high-affinity ligands for the Erbin PDZ domain; Vaccaro, P., Brannetti, B., Montecchi-Palazzi, L., Philipp, S., Citterich, M.H., Cesareni, G., Dente, L., Distinct binding specificity of the multiple PDZ domains of INADL, a human protein with homology to INAD from Drosophila melanogaster (2001) J. Biol. Chem., 276, pp. 42122-42130; Skelton, N.J., Koehler, M.F.T., Zobel, K., Wong, W.L., Yeh, S., Pisabarro, M.T., Yin, J.P., Sidhu, S.S., Origins of PDZ domain ligand specificity: Structure determination and mutagenesis of the Erbin PDZ domain (2002) J Biol Chem, , in press; Aarts, M., Liu, Y., Liu, L., Besshoh, S., Arundine, M., Gurd, J.W., Wang, Y.-T., Tymianski, M., Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions (2002) Science, 298, pp. 846-850. , This report demonstrates that PDZ domains may be valid therapeutic targets, and furthermore, that peptide ligands may be useful for target validation in vivo. Peptides were used to disrupt the interaction between PSD-95 PDZ2 and the NMDA receptor in the brains of live rats. This dissociated the NMDA receptor from downstream neurotoxic signaling but, importantly, did not block NMDA receptor functions that mediate essential neuronal excitation. As a result, treated animals were protected from focal ischaemic brain damage during stroke, without suffering from the deleterious effects associated with blocking the NMDA receptor; Macias, M.J., Wiesner, S., Sudol, M., WW and SH3 domains, two different scaffolds to recognize proline-rich ligands (2002) FEBS Lett., 513, pp. 30-37; Mayer, B.J., SH3 domains: Complexity in moderation (2001) J. Cell. Sci., 14, pp. 1253-1263; Federov, A.A., Fedorov, E., Gertler, F., Almo, S.C., Structure of EVH1, a novel prolin-rich ligand-binding module involved in cytoskeletal dynamics and neural function (1999) Nat. Struct. Biol., 6, pp. 661-665; Rickles, R.J., Botfield, M.C., Zhou, X.-M., Henry, P.A., Brugge, J.S., Zoller, M.J., Phage display selection of ligand residues important for Src homology 3 domain binding specificity (1995) Proc. Natl. Acad. Sci. USA, 92, pp. 10909-10913; Sparks, A.B., Rider, J.E., Hoffman, N.G., Fowlkes, D.M., Quilliam, L.A., Kay, B.K., Distinct ligand preferences of Src homology 3 domains from Src, Yes, Abl, Cortactin, p53bp2, PLCγ, Crk, and Grb2 (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 1540-1544; Mongiovi, A.M., Romano, P.R., Panni, S., Mendoza, M., Wong, W.T., Musacchio, A., Cesareni, G., Di Fiore, P.P., A novel peptide-SH3 interaction (1999) EMBO J., 18, pp. 5300-5309; Cestra, G., Castagnoli, L., Dente, L., Minenkova, O., Petrelli, A., Migone, N., Hoffmuller, U., Cesareni, G., The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity (1999) J. Biol. Chem., 274, pp. 32001-32007; Fazi, B., Cope, M.J.T.V., Douangamath, A., Ferracuti, S., Schirwitz, K., Zucconi, A., Drubin, D.G., Castagnoli, L., Unusual binding properties of the SH3 domain of the yeast actin-binding protein Abp1: Structural and functional analysis (2002) J. Biol. Chem., 277, pp. 5290-5298; Sparks, A.B., Quilliam, L.A., Thorn, J.M., Der, C.J., Kay, B.K., Identification and characterization of Src SH3 ligands from phage-displayed random peptide libraries (1994) J. Biol. Chem., 269, pp. 23853-23856; Rickles, R.J., Botfield, M.C., Weng, Z., Taylor, J.A., Green, O.M., Brugge, J.S., Zoller, M.J., Identification of Src, Fyn, Lyn, PI3K and Abl SH3 domain ligands using phage display libraries (1994) EMBO J., 13, pp. 5598-5604; Linn, H., Ermekova, K.S., Rentschler, S., Sparks, A.B., Kay, B.K., Sudol, M., Using molecular repertoires to identify high-affinity peptide ligands of the WW domain of human and mouse YAP (1997) Biol. Chem., 78, pp. 531-537; Kasanov, J., Pirozzi, G., Uveges, A.J., Kay, B.K., Characterizing class I WW domains defines key specificity determinants and generates mutant domains with novel specificities (2001) Chem. Biol., 8, pp. 231-241; Tong, A.H.Y., Drees, B., Nardelli, G., Bader, G.D., Brannetti, B., Castagnoli, L., Evangelista, M., Paoluzi, S., A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules (2002) Science, 295, pp. 321-324. , This work describes the integration of phage display data with yeast-two-hybrid data to produce high quality interaction predictions on a large scale. With the aid of computational methods, orthogonal datasets of genome-wide, putative interaction networks for 20 yeast SH3 domains were filtered against each other to produce a much smaller overlap network containing few false positives. The successful integration of data from different methods is certain to play an increasingly important role in functional genomics and proteomics; Legrain, P., Protein domain networking (2002) Nat. Biotechnol., 20, pp. 128-129; Hiipakka, M., Poikonen, K., Saksela, K., SH3 domains with high affinity and engineered ligand specificities targeted to HIV-1 Nef (1999) J. Mol. Biol., 293, pp. 1097-1106; Panni, S., Dente, L., Cesareni, G., In vitro evolution of recognition specificity mediated by SH3 domains reveals target recognition rules (2002) J. Biol. Chem., 277, pp. 21666-21674. , The authors produced an SH3 domain library designed to resemble the binding surfaces of natural SH3 domains. Such repertoires should be useful in generating not only binding domains for peptides of interest but, perhaps more importantly, they may help to identify natural SH3 domains that bind particular natural proline-rich ligands. In combination with data from peptide-phage libraries, these data may reveal general recognition rules for SH3 domain-ligand interactions","Sidhu, S.S.; Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States; email: sidhu@gene.com",,,,,,,,13675931,,COCBF,10.1016/S1367-5931(02)00011-X,12547433,"English","Curr. Opin. Chem. Biol.",Review,Scopus
"Bader G.D., Hogue C.W.V.","An automated method for finding molecular complexes in large protein interaction networks",2003,"BMC Bioinformatics",4,, 2,,,27,186,"http://www.scopus.com/inward/record.url?eid=2-s2.0-2942552459&partnerID=40&md5=79fe27abb7ff1291201e2c9da03829ba","Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ont. M5G 1X5, Canada; Memorial Sloan-Kettering Cancer Ctr., 1275 York Avenue, New York, NY 10021, United States; Dept. of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada","Bader, G.D., Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ont. M5G 1X5, Canada, Memorial Sloan-Kettering Cancer Ctr., 1275 York Avenue, New York, NY 10021, United States, Dept. of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Hogue, C.W.V., Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ont. M5G 1X5, Canada, Dept. of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada","Background: Recent advances in proteomics technologies such as two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of biomolecular interaction networks. Initial mapping efforts have already produced a wealth of data. As the size of the interaction set increases, databases and computational methods will be required to store, visualize and analyze the information in order to effectively aid in knowledge discovery. Results: This paper describes a novel graph theoretic clustering algorithm, ""Molecular Complex Detectio"" (MCODE), that detects densely connected regions in large protein-protein interaction networks that may represent molecular complexes. The method is based on vertex weighting by local neighborhood density and outward traversal from a locally dense seed protein to isolate the dense regions according to given parameters. The algorithm has the advantage over other graph clustering methods of having a directed mode that allows fine-tuning of clusters of interest without considering the rest of the network and allows examination of cluster interconnectivity, which is relevant for protein networks. Protein interaction and complex information from the yeast Saccharomyces cerevisiae was used for evaluation. Conclusion: Dense regions of protein interaction networks can be found, based solely on connectivity data, many of which correspond to known protein complexes. The algorithm is not affected by a known high rate of false positives in data from high-throughput interaction techniques. © 2003 Bader and Hogue; licensee BioMed Central Ltd.",,"algorithm; amino acid sequence; article; automation; cluster analysis; computer program; controlled study; mass spectrometry; nonhuman; phage display; protein protein interaction; proteomics; Saccharomyces cerevisiae; two hybrid system; Saccharomyces; Saccharomyces cerevisiae",,,"Mac OS X; Molecular Complex Detection; Pajek; UNIX; Windows",,,"Fields, S., Proteomics. Proteomics in genomeland (2001) Science, 291, pp. 1221-1224; Uetz, P., Giot, L., Cagney, G., Mansfield, T.A., Judson, R.S., Knight, J.R., A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae (2000) Nature, 403, pp. 623-627; Ito, T., Chiba, T., Ozawa, R., Yoshida, M., Hattori, M., Sakaki, Y., A comprehensive two-hybrid analysis to explore the yeast protein interactome (2001) Proc. Natl. Acad. Sci. U. S. A., 98, pp. 4569-4574; Drees, B.L., Sundin, B., Brazeau, E., Caviston, J.P., Chen, G.C., Guo, W., A protein interaction map for cell polarity development (2001) J. Cell Biol., 154, pp. 549-571; Fromont-Racine, M., Mayes, A.E., Brunet-Simon, A., Rain, J.C., Colley, A., Dix, I., Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins (2000) Yeast, 17, pp. 95-110; Ho, Y., Gruhler, A., Heilbut, A., Bader, G.D., Moore, L., Adams, S.L., Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry (2002) Nature, 415, pp. 180-183; Gavin, A.C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Functional organization of the yeast proteome by systematic analysis of protein complexes (2002) Nature, 415, pp. 141-147; Christendat, D., Yee, A., Dharamsi, A., Kluger, Y., Savchenko, A., Cort, J.R., Structural proteomics of an archaeon (2000) Nat. Struct. Biol., 7, pp. 903-909; Kim, S.K., Lund, J., Kiraly, M., Duke, K., Jiang, M., Stuart, J.M., A gene expression map for Caenorhabditis elegans (2001) Science, 293, pp. 2087-2092; Tong, A.H., Drees, B., Nardelli, G., Bader, G.D., Brannetti, B., Castagnoli, L., A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules (2002) Science, 295, pp. 321-324; Winzeler, E.A., Shoemaker, D.D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis (1999) Science, 285, pp. 901-906; Chervitz, S.A., Hester, E.T., Ball, C.A., Dolinski, K., Dwight, S.S., Harris, M.A., Using the Saccharomyces Genome Database (SGD) for analysis of protein similarities and structure (1999) Nucleic Acids Res., 27, pp. 74-78; Mewes, H.W., Frishman, D., Gruber, C., Geier, B., Haase, D., Kaps, A., MIPS: A database for genomes and protein sequences (2000) Nucleic Acids Res., 28, pp. 37-40; Costanzo, M.C., Crawford, M.E., Hirschman, J.E., Kranz, J.E., Olsen, P., Robertson, L.S., YPD, PombePD and WormPD: Model organism volumes of the BioKnowledge library, an integrated resource for protein information (2001) Nucleic Acids Res., 29, pp. 75-79; Bader, G.D., Donaldson, I., Wolting, C., Ouellette, B.F., Pawson, T., Hogue, C.W., BIND-The biomolecular interaction network database (2001) Nucleic Acids Res., 29, pp. 242-245; Xenarios, I., Salwinski, L., Duan, X.J., Higney, P., Kim, S.M., Eisenberg, D., DIP, the Database of Interacting Proteins: A research tool for studying cellular networks of protein interactions (2002) Nucleic Acids Res., 30, pp. 303-305; Takai-Igarashi, T., Nadaoka, Y., Kaminuma, T., A database for cell signaling networks (1998) J. 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Rev. Biophys. Biomol. Struct., 28, pp. 295-317; Batagelj, V., Mrvar, A., Pajek - Program for Large Network Analysis (1998) Connections, 2, pp. 47-57; Kamada, T., Kawai, S., An algorithm for drawing general indirect graphs (1989) Information Processing Letters, 31, pp. 7-15; Dobzhansky, T., Nothing in Biology Makes Sense Except in the Light of Evolution (1973) American Biology Teacher, 35, pp. 125-129; Gene ontology: Tool for the unification of biology (2000) Nat. Genet., 25, pp. 25-29. , The Gene Ontology Consortium; Pruitt, K.D., Maglott, D.R., RefSeq and LocusLink: NCBI genecentered resources (2001) Nucleic Acids Res., 29, pp. 137-140","Hogue, C.W.V.; Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ont. M5G 1X5, Canada; email: hogue@mshri.on.ca",,,,,,,,14712105,,BBMIC,10.1186/1471-2105-4-2,,"English","BMC Bioinform.",Article,Scopus
"Bader G.D., Hogue C.W.","An automated method for finding molecular complexes in large protein interaction networks.",2003,"BMC bioinformatics [electronic resource]",4,1,,2,,,496,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0037566556&partnerID=40&md5=95c65367b5dfd3421c441c38ff34a955","Samuel Lunenfeld Research Institute, Mt, Sinai Hospital, Toronto ON Canada M5G 1X5, Dept, of Biochemistry, University of Toronto, Toronto ON Canada M5S 1A8.","Bader, G.D., Samuel Lunenfeld Research Institute, Mt, Sinai Hospital, Toronto ON Canada M5G 1X5, Dept, of Biochemistry, University of Toronto, Toronto ON Canada M5S 1A8.; Hogue, C.W., Samuel Lunenfeld Research Institute, Mt, Sinai Hospital, Toronto ON Canada M5G 1X5, Dept, of Biochemistry, University of Toronto, Toronto ON Canada M5S 1A8.","BACKGROUND: Recent advances in proteomics technologies such as two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of biomolecular interaction networks. Initial mapping efforts have already produced a wealth of data. As the size of the interaction set increases, databases and computational methods will be required to store, visualize and analyze the information in order to effectively aid in knowledge discovery. RESULTS: This paper describes a novel graph theoretic clustering algorithm, ""Molecular Complex Detection"" (MCODE), that detects densely connected regions in large protein-protein interaction networks that may represent molecular complexes. The method is based on vertex weighting by local neighborhood density and outward traversal from a locally dense seed protein to isolate the dense regions according to given parameters. The algorithm has the advantage over other graph clustering methods of having a directed mode that allows fine-tuning of clusters of interest without considering the rest of the network and allows examination of cluster interconnectivity, which is relevant for protein networks. Protein interaction and complex information from the yeast Saccharomyces cerevisiae was used for evaluation. CONCLUSION: Dense regions of protein interaction networks can be found, based solely on connectivity data, many of which correspond to known protein complexes. The algorithm is not affected by a known high rate of false positives in data from high-throughput interaction techniques. The program is available from ftp://ftp.mshri.on.ca/pub/BIND/Tools/MCODE.",,"Saccharomyces cerevisiae protein; algorithm; article; biology; chemistry; cluster analysis; computer graphics; computer program; evaluation; macromolecule; metabolism; methodology; prediction and forecasting; protein analysis; proteomics; Algorithms; Cluster Analysis; Computational Biology; Computer Graphics; Macromolecular Substances; Predictive Value of Tests; Protein Interaction Mapping; Proteomics; Saccharomyces cerevisiae Proteins; Software Validation",,"Macromolecular Substances; Saccharomyces cerevisiae Proteins",,,,,"Bader, G.D.email: gary.bader@utoronto.ca",,,,,,,,14712105,,,,12525261,"English","BMC Bioinformatics",Article,Scopus
"Bader G.D., Betel D., Hogue C.W.V.","BIND: The Biomolecular Interaction Network Database",2003,"Nucleic Acids Research",31,1,,248,250,,567,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0037245913&partnerID=40&md5=88ac074107b4901734ce9f07c4c687e5","Department of Biochemistry, Samuel Lunenfeld Research Inst., University of Toronto, Toronto, Ont. M5G 1X5, Canada","Bader, G.D., Department of Biochemistry, Samuel Lunenfeld Research Inst., University of Toronto, Toronto, Ont. M5G 1X5, Canada; Betel, D., Department of Biochemistry, Samuel Lunenfeld Research Inst., University of Toronto, Toronto, Ont. M5G 1X5, Canada; Hogue, C.W.V., Department of Biochemistry, Samuel Lunenfeld Research Inst., University of Toronto, Toronto, Ont. M5G 1X5, Canada","The Biomolecular Interaction Network Database (BIND: http://bind.ca) archives biomolecular interaction, complex and pathway information. A web-based system is available to query, view and submit records. BIND continues to grow with the addition of individual submissions as well as interaction data from the PDB and a number of large-scale interaction and complex mapping experiments using yeast two hybrid, mass spectrometry, genetic interactions and phage display. We have developed a new graphical analysis tool that provides users with a view of the domain composition of proteins in interaction and complex records to help relate functional domains to protein interactions. An interaction network clustering tool has also been developed to help focus on regions of interest. Continued input from users has helped further mature the BIND data specification, which now includes the ability to store detailed information about genetic interactions. The BIND data specification is available as ASN.1 and XML DTD.",,"protein; Biomolecular Interaction Network Database; gene interaction; Internet; mass spectrometry; molecular interaction; peptide mapping; phage display; priority journal; protein analysis; protein database; protein domain; review; two hybrid system; Amino Acid Sequence; Animals; Computer Graphics; Databases, Protein; Macromolecular Substances; Protein Interaction Mapping; Protein Structure, Tertiary; Proteins; Sequence Alignment",,"protein, 67254-75-5; Macromolecular Substances; Proteins",,,,"Fields, S., Proteomics. Proteomics in genomeland (2001) Science, 291, pp. 1221-1224; Xenarios, I., Salwinski, L., Duan, X.J., Higney, P., Kirn, S.M., Eisenberg, D., DIP, the Database of Interacting Proteins: A research tool for studying cellular networks of protein interactions (2002) Nucleic Acids Res., 30, pp. 303-305; Zanzoni, A., Montecchi-Palazzi, L., Quondam, M., Ausiello, G., Helmer-Citterich, M., Cesareni, G., MINT: A Molecular INTeraction database (2002) FEBS Lett., 513, pp. 135-140; Bader, G.D., Donaldson, I., Wolting, C., Ouellette, B.F., Pawson, T., Hogue, C.W., BIND-the biomolecular interaction network database (2001) Nucleic Acids Res., 29, pp. 242-245; Bader, G.D., Hogue, C.W., BIND-a data specification for storing and describing biomolecular interactions, molecular complexes and pathways (2000) Bioinformatics, 16, pp. 465-477; Tong, A.H., Evangelista, M., Parsons, A.B., Xu, H., Bader, G.D., Page, N., Robinson, M., Bussey, H., Systematic genetic analysis with ordered arrays of yeast deletion mutants (2001) Science, 294, pp. 2364-2368; Ho, Y., Gruhler, A., Heilbut, A., Bader, G.D., Moore, L., Adams, S.L., Millar, A., Boutilier, K., Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry (2002) Nature, 415, pp. 180-183; Tong, A.H., Drees, B., Nardelli, G., Bader, G.D., Brannetti, B., Castagnoli, L., Evangelista, M., Paoluzi, S., A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules (2002) Science, 295, pp. 321-324; Westbrook, J., Feng, Z., Jain, S., Bhat, T.N., Thanki, N., Ravichandran, V., Gilliland, G.L., Greer, D.S., The Protein Data Bank: Unifying the archive (2002) Nucleic Acids Res., 30, pp. 245-248; Wang, Y., Anderson, J.B., Chen, J., Geer, L.Y., He, S., Hurwitz, D.I., Liebert, C.A., Marchler-Bauer, A., MMDB: Entrez's 3D-structure database (2002) Nucleic Acids Res., 30, pp. 249-252; Salama, J.J., Donaldson, I., Hogue, C.W., Automatic annotation of BIND molecular interactions from three-dimensional structures (2002) Biopolymers, 61, pp. 111-120; Schuler, G.D., Epstein, J.A., Ohkawa, H., Kans, J.A., Entrez: Molecular biology database and retrieval system (1996) Methods Enzymol., 266, pp. 141-162; Batagelj, V., Mrvar, A., Pajek-Program for large network analysis (1998) Connections, 2, pp. 47-57; Pawson, T., Protein modules and signalling networks (1995) Nature, 373, pp. 573-580; Marchler-Bauer, A., Panchenko, A.R., Shoemaker, B.A., Thiessen, P.A., Geer, L.Y., Bryant, S.H., CDD: A database of conserved domain alignments with links to domain three-dimensional structure (2002) Nucleic Acids Res., 30, pp. 281-283; Gavin, A.C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Cruciat, C.M., Functional organization of the yeast proteome by systematic analysis of protein complexes (2002) Nature, 415, pp. 141-147; Geor, L.Y., Domrachov, M., Lipman, D.J., Bryant, S.H., CDART: Protein Homology by Domain Architecture (2002) Genome Res., 12, pp. 1619-1623; Michalickova, K., Bader, G.D., Dumontier, M., Lieu, H.C., Betel, D., Issorlin, R., Hogue, C.W., SeqHound: Biological sequence and structure database as a platform for bioinformatics research (2002) BMC Bioinformatics, , in press","Hogue, C.W.V.; Department of Biochemistry, Samuel Lunenfeld Research Inst., University of Toronto, Toronto, Ont. M5G 1X5, Canada; email: hogue@mshri.on.ca",,,,,,,,03051048,,NARHA,10.1093/nar/gkg056,12519993,"English","Nucleic Acids Res.",Review,Scopus
"Michalickova K., Bader G.D., Dumontier M., Lieu H., Betel D., Isserlin R., Hogue C.W.V.","SeqHound: Biological sequence and structure database as a platform for bioinformatics research",2002,"BMC Bioinformatics",3,, 32,,,13,37,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0012787398&partnerID=40&md5=37e69a1b13692929f9452e56b952aad3","Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada","Michalickova, K., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada; Bader, G.D., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada; Dumontier, M., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada; Lieu, H., Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada; Betel, D., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, CanadaSamuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada, ; Isserlin, R., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, CanadaSamuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada, ; Hogue, C.W.V., Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, CanadaSamuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada, ","Background: SeqHound has been developed as an integrated biological sequence, taxonomy, annotation and 3-D structure database system. It provides a high-performance server platform for bioinformatics research in a locally-hosted environment. Results: SeqHound is based on the National Center for Biotechnology Information data model and programming tools. It offers daily updated contents of all Entrez sequence databases in addition to 3-D structural data and information about sequence redundancies, sequence neighbours, taxonomy, complete genomes, functional annotation including Gene Ontology terms and literature links to PubMed. SeqHound is accessible via a web server through a Perl, C or C++ remote API or an optimized local API. It provides functionality necessary to retrieve specialized subsets of sequences, structures and structural domains. Sequences may be retrieved in FASTA, GenBank, ASN.1 and XML formats. Structures are available in ASN.1, XML and PDB formats. Emphasis has been placed on complete genomes, taxonomy, domain and functional annotation as well as 3-D structural functionality in the API, while fielded text indexing functionality remains under development. SeqHound also offers a streamlined WWW interface for simple web-user queries. Conclusions: The system has proven useful in several published bioinformatics projects such as the BIND database and offers a cost-effective infrastructure for research. SeqHound will continue to develop and be provided as a service of the Blueprint Initiative at the Samuel Lunenfeld Research Institute. The source code and examples are available under the terms of the GNU public license at the Sourceforge site http://sourceforge.net/projects/slritools/ in the SLRI Toolkit. © 2002 Michalickova et al; licensee BioMed Central Ltd.","Local database resource; Sequence database; Structure database","access to information; article; bioinformatics; clinical research; computer interface; computer program; cost effectiveness analysis; GenBank; gene sequence; gene structure; genetic database; information processing; information retrieval; information system; Internet; licence; medical research; MEDLINE; protein domain; protein function; redundancy analysis; scientific literature; sequence database; structure activity relation; taxonomy; amino acid sequence; biological model; biology; chemical structure; classification; methodology; molecular genetics; nucleotide sequence; Amino Acid Sequence; Base Sequence; Computational Biology; Databases, Genetic; Information Storage and Retrieval; Internet; Models, Genetic; Models, Molecular; Molecular Sequence Data; Software; Structure-Activity Relationship",,,"SeqHound",,,"Schuler, G.D., Epstein, J.A., Ohkawa, H., Kans, J.A., Entrez: Molecular biology database and retrieval system (1996) Methods Enzymol., 266, pp. 141-162; Stoesser, G., Baker, W., van den, B.A., Camon, E., Garcia-Pastor, M., Kanz, C., Kulikova, T., Lombard, V., The EMBL Nucleotide Sequence Database (2002) Nucleic Acids Res., 30, pp. 21-26; Bader, G.D., Hogue, C.W., BIND-a data specification for storing and describing biomolecular interactions, molecular complexes and pathways (2000) Bioinformatics, 16, pp. 465-477; Bader, G.D., Donaldson, I., Wolting, C., Ouellette, B.F., Pawson, T., Hogue, C.W., BIND-The biomolecular interaction network database (2001) Nucleic Acids Res., 29, pp. 242-245; Betel, D., Hogue, C.W., Kangaroo - A pattern-matching program for biological sequences (2002) BMC Bioinformatics, 3, p. 20; Michalickova, K., Dharsee, M., Hogue, C.W.V., Sequence analysis on a 216 processor Beowulf cluster (2000), 4, pp. 111-119. , 4th Annual Linux Showcase and Conference, AtlantaAltschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J., Basic local alignment search tool (1990) J. Mol. Biol., 215, pp. 403-410; Dumontier, M., Hogue, C.W., NBLAST: A cluster variant of BLAST for NxN comparisons (2002) BMC Bioinformatics, 3, p. 13; Benson, D.A., Karsch-Mizrachi, I., Lipman, D.J., Ostell, J., Rapp, B.A., Wheeler, D.L., GenBank (2002) Nucleic Acids Res., 30, pp. 17-20; Pruitt, K.D., Maglott, D.R., RefSeq and LocusLink: NCBI genecentered resources (2001) Nucleic Acids Res., 29, pp. 137-140; Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., The Protein Data Bank (2000) Nucleic Acids Res., 28, pp. 235-242; Bairoch, A., Apweiler, R., The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 (2000) Nucleic Acids Res., 28, pp. 45-48; Boguski, M.S., Lowe, T.M., Tolstoshev, C.M., dbEST database for ""expressed sequence tags"" (1993) Nat. Genet., 4, pp. 332-333; Wang, Y., Anderson, J.B., Chen, J., Geer, L.Y., He, S., Hurwitz, D.I., Liebert, C.A., Marchler-Bauer, A., MMDB: Entrez's 3D-structure database (2002) Nucleic Acids Res., 30, pp. 249-252; Wu, C.H., Huang, H., Arminski, L., Castro-Alvear, J., Chen, Y., Hu, Z.Z., Ledley, R.S., Orcutt, B.C., The Protein Information Resource: An integrated public resource of functional annotation of proteins (2002) Nucleic Acids Res., 30, pp. 35-37; Marchler-Bauer, A., Panchenko, A.R., Shoemaker, B.A., Thiessen, P.A., Geer, L.Y., Bryant, S.H., CDD: A database of conserved domain alignments with links to domain three-dimensional structure (2002) Nucleic Acids Res., 30, pp. 281-283; The Gene Ontology Consortium Creating the gene ontology resource: Design and implementation (2001) Genome Res., 11, pp. 1425-1433; Ostell, J.M., Kans, J.A., The NCBI data model (1998) Methods Biochem. Anal., 39, pp. 121-144; Bateman, A., Birney, E., Cerruti, L., Durbin, R., Etwiller, L., Eddy, S.R., Griffiths-Jones, S., Sonnhammer, E.L., The Pfam protein families database (2002) Nucleic Acids Res., 30, pp. 276-280; Letunic, I., Goodstadt, L., Dickens, N.J., Doerks, T., Schultz, J., Mott, R., Ciccarelli, F., Bork, P., Recent improvements to the SMART domain-based sequence annotation resource (2002) Nucleic Acids Res., 30, pp. 242-244; Higgins, D.G., Sharp, P.M., CLUSTAL: A package for performing multiple sequence alignment on a microcomputer (1988) Gene, 73, pp. 237-244; Thompson, J.D., Higgins, D.G., Gibson, T.J., CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice (1994) Nucleic Acids Res., 22, pp. 4673-4680; Chung, S.Y., Wong, L., Kleisli: A new tool for data integration in biology (1999) Trends Biotechnol., 17, pp. 351-355","Hogue, C.W.V.; Department of Biochemistry, University of Toronto, Toronto, Ont. M5S 1A8, Canada; email: hogue@mshri.on.ca",,,,,,,,14712105,,BBMIC,10.1186/1471-2105-3-32,12401134,"English","BMC Bioinform.",Article,Scopus
"Bader G.D., Hogue C.W.V.","Analyzing yeast protein-protein interaction data obtained from different sources",2002,"Nature Biotechnology",20,10,,991,997,,318,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0036789265&partnerID=40&md5=ae3c9cbcba4019239ba41b2d4892c98d","Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ont. MSG 1X5, Canada","Bader, G.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ont. MSG 1X5, Canada; Hogue, C.W.V., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ont. MSG 1X5, Canada","High-throughput methods for detecting protein interactions, such as mass spectrometry and yeast two-hybrid assays, continue to produce vast amounts of data that may be exploited to infer protein function and regulation. As this article went to press, the pool of all published interaction information on Saccharomyces cerevisiae was 15,143 interactions among 4,825 proteins, and power-law scaling supports an estimate of 20,000 specific protein interactions. To investigate the biases, overlaps, and complementarities among these data, we have carried out an analysis of two high-throughput mass spectrometry (HMS)-based protein interaction data sets from budding yeast, comparing them to each other and to other interaction data sets. Our analysis reveals 198 interactions among 222 proteins common to both data sets, many of which reflect large multiprotein complexes. It also indicates that a ""spoke"" model that directly pairs bait proteins with associated proteins is roughly threefold more accurate than a ""matrix"" model that connects all proteins. In addition, we identify a large, previously unsuspected nucleolar complex of 148 proteins, including 39 proteins of unknown function. Our results indicate that existing large-scale protein interaction data sets are nonsaturating and that integrating many different experimental data sets yields a clearer biological view than any single method alone.",,"Bioassay; Complexation; Mass spectrometry; Proteins; Protein interactions; Yeast; fungal protein; accuracy; article; controlled study; mass spectrometry; nonhuman; priority journal; protein function; protein interaction; protein protein interaction; publishing; regulatory mechanism; Saccharomyces cerevisiae; yeast; Chromatography, Liquid; Database Management Systems; Databases, Protein; Genome, Fungal; Macromolecular Substances; Mass Spectrometry; Multiprotein Complexes; Protein Interaction Mapping; Proteome; Reproducibility of Results; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sensitivity and Specificity; Sequence Alignment; Sequence Analysis, Protein; Species Specificity; Saccharomyces; Saccharomyces cerevisiae; Saccharomycetales; Trixis",,"Macromolecular Substances; Multiprotein Complexes; Proteome; Saccharomyces cerevisiae Proteins",,,,"Fields, S., Proteomics. Proteomics in genomeland (2001) Science, 291, pp. 1221-1224; Pawson, T., Gish, G.D., Nash, P., SH2 domains, interaction modules and cellular wiring (2001) Trends Cell Biol., 11, pp. 504-511; Marcotte, E.M., Detecting protein function and protein-protein interactions from genome sequences (1999) Science, 285, pp. 751-753; Gavin, A.C., Functional organization of the yeast proteome by systematic analysis of protein complexes (2002) Nature, 415, pp. 141-147; Ho, Y., Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry (2002) Nature, 415, pp. 180-183; Pandey, A., Mann, M., Proteomics to study genes and genomes (2000) Nature, 405, pp. 837-846; Von Mering, C., Comparative assessment of large-scale data sets of proteinprotein interactions (2002) Nature, 417, pp. 399-403; Bader, G.D., BIND-The biomolecular interaction network database (2001) Nucleic Acids Res, 29, pp. 242-245; Ito, T., A comprehensive two-hybrid analysis to explore the yeast protein interactome (2001) Proc. Natl. Acad. Sci. USA, 98, pp. 4569-4574; Uetz, P., A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae (2000) Nature, 403, pp. 623-627; Tong, A.H., A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules (2002) Science, 295, pp. 321-324; Drees, B.L., A protein interaction map for cell polarity development (2001) J. Cell Biol., 154, pp. 549-571; Fromont-Facine, M., Genome-wide protein interaction screens reveal functional networks involving Sm-like proteins (2000) Yeast, 17, pp. 95-110; Ashburner, M., Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium (2000) Nat. Genet., 25, pp. 25-29; Mewes, H.W., MIPS: A database for genomes and protein sequences (2000) Nucleic Acids Res., 28, pp. 37-40; Costanzo, M.C., YPD, PombePD and WormPD: Model organism volumes of the BioKnowledge library, an integrated resource for protein information (2001) Nucleic Acids Res., 29, pp. 75-79; Andersen, J.S., Directed proteomic analysis of the human nucleolus (2002) Curr. Biol., 12, pp. 1-11; Harnpicharnchai, P., Composition and functional characterization of yeast 66S ribosome assembly intermediates (2001) Mol. Cell, 8, pp. 505-515; Schwikowski, B., Uetz, P., Fields, S., A network of protein-protein interactions in yeast (2000) Nat. Biotechnol., 18, pp. 1257-1261; Jeong, H., Tombor, B., Albert, R., Oltvai, Z.N., Barabasi, A.L., The large-scale organization of metabolic networks (2000) Nature, 407, pp. 651-654; Jeong, H., Mason, S.P., Barabasi, A.L., Oltvai, Z.N., Lethality and centrality in protein networks (2001) Nature, 411, pp. 41-42; Pruitt, K.D., Maglott, D.R., RefSeq and LocusLink: NCBI gene-centered resources (2001) Nucleic Acids Res., 29, pp. 137-140; Chervitz, S.A., Using the Saccharomyces Genome Database (SGD) for analysis of protein similarities and structure (1999) Nucleic Acids Res., 27, pp. 74-78; Norris, V., Hypothesis: Hyperstructures regulate bacterial structure and the cell cycle (1999) Biochimie, 81, pp. 915-920; Xenarios, I., DIP, the Database of Interacting Proteins: A research tool for studying cellular networks of protein interactions (2002) Nucleic Acids Res., 30, pp. 303-305; Ge, H., Liu, Z., Church, G.M., Vidal, M., Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae (2001) Nat. Genet., 29, pp. 482-486; Olson, M.O., Dundr, M., Szebeni, A., The nucleolus: An old factory with unexpected capabilities (2000) Trends Cell Biol., 10, pp. 189-196; Visintin, R., Amon, A., The nucleolus: The magician's hat for cell cycle tricks (2000) Curr. Opin. Cell. Biol., 12, p. 752","Hogue, C.W.V.; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ont. MSG 1X5, Canada; email: hogue@mshri.on.ca",,,,,,,,10870156,,NABIF,10.1038/nbt1002-991,12355115,"English","Nat. Biotechnol.",Article,Scopus
"Tong A.H.Y., Drees B., Nardelli G., Bader G.D., Brannetti B., Castagnoli L., Evangelista M., Ferracuti S., Nelson B., Paoluzi S., Quondam M., Zucconi A., Hogue C.W.V., Fields S., Boone C., Cesareni G.","A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules",2002,"Science",295,5553,,321,324,,409,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0037059461&partnerID=40&md5=18dd0e47d9d987d66fb9cb38860bffe5","Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States","Tong, A.H.Y., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Drees, B., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Nardelli, G., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Bader, G.D., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Brannetti, B., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Castagnoli, L., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Evangelista, M., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Ferracuti, S., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Nelson, B., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Paoluzi, S., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Quondam, M., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Zucconi, A., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Hogue, C.W.V., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Fields, S., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Boone, C., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; Cesareni, G., Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States","Peptide recognition modules mediate many protein-protein interactions critical for the assembly of macromolecular complexes. Complete genome sequences have revealed thousands of these domains, requiring improved methods for identifying their physiologically relevant binding partners. We have developed a strategy combining computational prediction of interactions from phage-display ligand consensus sequences with large-scale two-hybrid physical interaction tests. Application to yeast SH3 domains generated a phage-display network containing 394 interactions among 206 proteins and a two-hybrid network containing 233 interactions among 145 proteins. Graph theoretic analysis identified 59 highly likely interactions common to both networks. Las17 (Bee1), a member of the Wiskott-Aldrich Syndrome protein (WASP) family of actin-assembly proteins, showed multiple SH3 interactions, many of which were confirmed in vivo by coimmunoprecipitation.",,"Genes; Macromolecules; Physiology; Yeast; Peptide recognition; Proteins; actin; peptide; protein; protein Las17; unclassified drug; Wiskott Aldrich syndrome protein; protein; article; calculation; experiment; gene sequence; immunoprecipitation; macromolecule; molecular recognition; nonhuman; phage display; priority journal; protein assembly; protein domain; protein protein interaction; two hybrid system; yeast; Algorithms; Amino Acid Motifs; Amino Acid Sequence; Binding Sites; Computational Biology; Consensus Sequence; Cytoskeletal Proteins; Databases, Genetic; Databases, Protein; Fungal Proteins; Ligands; Molecular Sequence Data; Peptide Library; Peptides; Protein Binding; Protein Structure, Tertiary; Proteins; Proteome; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Software; src Homology Domains; Two-Hybrid System Techniques; Wiskott-Aldrich Syndrome Protein; Vespidae",,"Cytoskeletal Proteins; Fungal Proteins; LAS17 protein, S cerevisiae; Ligands; Peptide Library; Peptides; Proteins; Proteome; Saccharomyces cerevisiae Proteins; Wiskott-Aldrich Syndrome Protein",,,,"Pawson, T., Scott, J.D., (1997) Science, 278, p. 2075; Ren, R., Mayer, B.J., Cicchetti, P., Baltimore, D., (1993) Science, 259, p. 1157; Salcini, A.E., (1997) Genes Dev., 11, p. 2239; Moran, M.F., (1990) Proc. 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Cell Biol., 154, p. 549; notenotenotenoteMochida, J., Yamamoto, T., Fujimura-Kamada, K., Tanaka, K., personal communicationWinzeler, E.H., (1999) Science, 285, p. 901; note","Fields, S.; Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195, United States; email: fields@u.washington.edu",,,,,,,,00368075,,SCIEA,10.1126/science.1064987,11743162,"English","Science",Article,Scopus
"Ho Y., Gruhler A., Heilbut A., Bader G.D., Moore L., Adams S.-L., Millar A., Taylor P., Bennett K., Boutilier K., Yang L., Wolting C., Donaldson I., Schandorff S., Shewnarane J., Vo M., Taggart J., Goudreault M., Muskat B., Alfarano C., Dewar D., Lin Z., Michalickova K., Willems A.R., Sassi H., Nielsen P.A., Rasmussen K.J., Andersen J.R., Johansen L.E., Hansen L.H., Jespersen H., Podtelejnikov A., Nielsen E., Crawford J., Poulsen V., Sorensen B.D., Matthiesen J., Hendrickson R.C., Gleeson F., Pawson T., Moran M.F., Durocher D., Mann M., Hogue C.W.V., Figeys D., Tyers M.","Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry",2002,"Nature",415,6868,,180,183,,2192,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0037050004&partnerID=40&md5=612757abbbcfaa34bfc0aeaf82c6c316","MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada","Ho, Y., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Gruhler, A., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Heilbut, A., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Bader, G.D., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Moore, L., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Adams, S.-L., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Millar, A., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Taylor, P., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Bennett, K., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Boutilier, K., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Yang, L., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Wolting, C., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Donaldson, I., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Schandorff, S., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Shewnarane, J., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Vo, M., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Taggart, J., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Goudreault, M., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Muskat, B., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Alfarano, C., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Dewar, D., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Lin, Z., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Michalickova, K., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Willems, A.R., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Sassi, H., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Nielsen, P.A., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Rasmussen, K.J., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Andersen, J.R., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Johansen, L.E., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Hansen, L.H., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Jespersen, H., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Podtelejnikov, A., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Nielsen, E., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Crawford, J., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Poulsen, V., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Sørensen, B.D., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Matthiesen, J., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Hendrickson, R.C., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Gleeson, F., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Pawson, T., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Moran, M.F., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Durocher, D., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Mann, M., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Hogue, C.W.V., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Figeys, D., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; Tyers, M., MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada","The recent abundance of genome sequence data has brought an urgent need for systematic proteomics to decipher the encoded protein networks that dictate cellular function. To date, generation of large-scale protein-protein interaction maps has relied on the yeast two-hybrid system, which detects binary interactions through activation of reporter gene expression. With the advent of ultrasensitive mass spectrometric protein identification methods, it is feasible to identify directly protein complexes on a proteome-wide scale. Here we report, using the budding yeast Saccharomyces cerevisiae as a test case, an example of this approach, which we term high-throughput mass spectrometric protein complex identification (HMS-PCI). Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. Numerous protein complexes were identified, including many new interactions in various signalling pathways and in the DNA damage response. Comparison of the HMS-PCI data set with interactions reported in the literature revealed an average threefold higher success rate in detection of known complexes compared with large-scale two-hybrid studies. Given the high degree of connectivity observed in this study, even partial HMS-PCI coverage of complex proteomes, including that of humans, should allow comprehensive identification of cellular networks.",,"DNA sequences; Mass spectrometry; Yeast; Genome sequences; Proteins; fungal protein; proteome; protein; article; cell function; complex formation; DNA damage; gene sequence; mass spectrometry; nonhuman; priority journal; protein analysis; protein protein interaction; Saccharomyces cerevisiae; signal transduction; two hybrid system; yeast; Amino Acid Sequence; Cell Cycle Proteins; Cloning, Molecular; DNA Damage; DNA Repair; DNA, Fungal; Humans; Macromolecular Substances; Mass Spectrometry; Molecular Sequence Data; Phosphoric Monoester Hydrolases; Protein Binding; Protein Kinases; Proteome; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sequence Alignment; Signal Transduction; Saccharomyces; Saccharomyces cerevisiae; Saccharomycetales; Trixis",,"Cell Cycle Proteins; DNA, Fungal; DUN1 protein, S cerevisiae, EC 2.7.1.-; Macromolecular Substances; Phosphoric Monoester Hydrolases, EC 3.1.3.-; Protein Kinases, EC 2.7.1.37; Proteome; Saccharomyces cerevisiae Proteins",,,,"Pawson, T., Nash, P., Protein-protein interactions define specificity in signal transduction (2000) Genes Dev., 14, pp. 1027-1047; Fields, S., Song, O., A novel genetic system to detect protein-protein interactions (1989) Nature, 340, pp. 245-246; Uetz, P., A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae (2000) Nature, 403, pp. 623-627; Ito, T., A comprehensive two-hybrid analysis to explore the yeast protein interactome (2001) Proc. Natl Acad. Sci. USA, 98, pp. 4569-4574; Neubauer, G., Identification of the proteins of the yeast U 1 small nuclear ribonucleoprotein complex by mass spectrometry (1997) Proc. Natl Acad. Sci. USA, 94, pp. 385-390; Mann, M., Hendrickson, R.C., Pandey, A., Analysis of proteins and proteomes by mass spectrometry (2001) Annu. Rev. Biochem., 10, pp. 437-473; Gustin, M.C., Albertyn, J., Alexander, M., Davenport, K., MAP kinase pathways in the yeast Saccharomyces cerevisiae (1998) Microbiol. Mol. Biol. Rev., 62, pp. 1264-1300; Morgan, D.O., Cyclin-dependent kinases: Engines, clocks, and microprocessors (1997) Annu. Rev. Cell. Dev. Biol., 13, pp. 261-291; McMillan, J.N., The morphogenesis checkpoint in Saccharomyces cerevisiae: Cell cycle control of Swelp degradation by Hsl 1p and Hsl7p (1999) Mol. Cell. Biol., 19, pp. 6929-6939; Philips, J., Herskowitz, I., Identification of Kel1p, a kelch domain-containing protein involved in cell fusion and morphology in Saccharomyces cerevisiae (1998) J. Cell. Biol., 143, pp. 375-389; Jorgensen, P., Tyers, M., The fork'ed path to mitosis (2000) Genome Biol., 1, pp. 10221-10224; Alexandru, G., Uhlmann, F., Mechtler, K., Poupart, M., Nasmyth, K., Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc 5 kinase regulates sister chromatid separation in yeast (2001) Cell, 105, pp. 459-472; Zhou, B.B., Elledge, S.J., The DNA damage response: Putting checkpoints in perspective (2000) Nature, 408, pp. 433-439; Prakash, S., Prakash, L., Nucleotide excision repair in yeast (2000) Mutat. Res., 451, pp. 13-24; Thelen, M.P., Venclovas, C., Fidelis, K., A sliding clamp model for the Rad 1 family of cell cycle checkpoint proteins (1999) Cell, 96, pp. 769-770; Koegl, M., A novel ubiquitination factor, E 4, is involved in multiubiquitin chain assembly (1999) Cell, 96, pp. 635-644; Ortolan, T.G., The DNA repair protein Rad23 is a negative regulator of multi-ubiquitin chain assembly (2000) Nature Cell Biol., 2, pp. 601-608; Tyers, M., Rottapel, R., VHL: A very hip ligase (1999) Proc. Natl. Acad. Sci. USA, 96, pp. 12230-12232; Emili, A., Schietz, D.M., Yates, J.R., Hartwell, L.H., Dynamic interaction of DNA damage checkpoint protein Rad 53 with chromatin assembly factor Asf1 (2001) Mol. Cell, 7, pp. 13-20; Hu, F., Alcasabas, A.A., Elledge, S.J., Asf 1 links Rad53 to control of chromatin assembly (2001) Genes Dev., 15, pp. 1061-1066; Marsolier, M.C., Roussel, P., Leroy, C., Mann, C., Involvement of the PP2C-like phosphatase Ptc 2p in the DNA checkpoint pathways of Saccharomyces cerevisiae (2000) Genetics, 154, pp. 1523-1532; Durocher, D., Henckel, J., Fersht, A.R., Jackson, S.P., The FHA domain is a modular phosphopeptide recognition motif (1999) Mol. Cell, 4, pp. 387-394; Zhao, X., Chabes, A., Domkin, V., Thelander, L., Rothstein, R., The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad 53 kinase cascade during growth and in response to DNA damage (2001) EMBO J., 20, pp. 3544-3553; Beaudenon, S.L., Huacani, M.R., Wang, G., McDonnell, D.P., Huibregtse, J.M., Rsp5 ubiquitin-protein ligase mediates DNA damage-induced degradation of the large subunit of RNA polymerase II in Saccharomyces cerevisiae (1999) Mol. Cell. Biol., 19, pp. 6972-6979; Bader, G., BIND - The biomolecular interaction network database (2001) Nucleic Acids Res., 29, pp. 242-245; Mewes, H.W., MIPS: A database for genomes and protein sequences (2000) Nucleic Acids Res., 28, pp. 37-40; Jeong, H., Tombor, B., Albert, R., Oltvai, Z.N., Barabasi, A.L., The large-scale organization of metabolic networks (2000) Nature, 407, pp. 651-654; Chervitz, S.A., Comparison of the complete protein sets of worm and yeast: Orthology and divergence (1998) Science, 282, pp. 2022-2028; Zhu, H., Global analysis of protein activities using proteome chips (2001) Science, 293, pp. 2101-2105; Wilm, M., Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry (1996) Nature, 379, pp. 466-469","Figeys, D.; MDS Proteomics, 251 Attwell Drive, Toronto, Ont. M9W 7H4, Canada; email: dfigeys@mdsp.com",,,,,,,,00280836,,NATUA,10.1038/415180a,11805837,"English","Nature",Article,Scopus
"Tong A.H.Y., Evangelista M., Parsons A.B., Xu H., Bader G.D., Page N., Robinson M., Raghibizadeh S., Hogue C.W.V., Bussey H., Andrews B., Tyers M., Boone C.","Systematic genetic analysis with ordered arrays of yeast deletion mutants",2001,"Science",294,5550,,2364,2368,,987,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0035861532&partnerID=40&md5=657ee95d11c5632631929ebff81208b5","Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada","Tong, A.H.Y., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Evangelista, M., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Parsons, A.B., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Xu, H., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Bader, G.D., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Pagé, N., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Robinson, M., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Raghibizadeh, S., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Hogue, C.W.V., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Bussey, H., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Andrews, B., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Tyers, M., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; Boone, C., Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada","In Saccharomyces cerevisiae, more than 80% of the ∼6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (sga) analysis, in which a query mutation is crossed to an array of∼4700 deletion mutants. Inviable double-mutant meiotic progeny:identify functional relationships between genes. Sga analysis of genes with roles in cytoskeletal organization (bni1, Arp2, Arc40, Bim1), Dna synthesis and repair (sgs1, Rad27), or uncharacterized functions (bbc1, Nbp2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.",,"Genes; Yeast; Mutants; Genetic engineering; genetics; yeast; article; deletion mutant; DNA repair; DNA synthesis; gene function; gene mutation; gene sequence; genetic analysis; nonhuman; phenotype; priority journal; Saccharomyces cerevisiae; sequence analysis; Carrier Proteins; Cell Cycle Proteins; Cell Polarity; Computational Biology; Crosses, Genetic; Cytoskeletal Proteins; Cytoskeleton; Databases, Genetic; DNA Helicases; DNA Repair; DNA, Fungal; Endodeoxyribonucleases; Flap Endonucleases; Fungal Proteins; Gene Deletion; Genes, Essential; Genes, Fungal; Genetic Markers; Genetic Techniques; Genome, Fungal; Microfilament Proteins; Microtubule Proteins; Mitosis; Recombination, Genetic; Robotics; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae",,"BIM1 protein, S cerevisiae; Bni1 protein, S cerevisiae; BNR1 protein, S cerevisiae; Carrier Proteins; Cell Cycle Proteins; Cytoskeletal Proteins; DNA Helicases, EC 3.6.1.-; DNA, Fungal; Endodeoxyribonucleases, EC 3.1.-; Flap Endonucleases, EC 3.1.-; Fungal Proteins; Genetic Markers; Microfilament Proteins; Microtubule Proteins; RAD27 protein, S cerevisiae, EC 3.1.11.5; Saccharomyces cerevisiae Proteins; SGS1 protein, S cerevisiae, EC 5.99.-",,,,"Winzeler, E.A., (1999) Science, 285, p. 901; Hartman IV, J.L., Garvik, B., Hartwell, L., (2001) Science, 291, p. 1001; Wagner, A., (2000) Nature Genet., 24, p. 355; Novick, P., Osmond, B.C., Botstein, D., (1989) Genetics, 121, p. 659; Guarente, L., (1993) Trends Genet., 9, p. 362; Bender, A., Pringle, A.J.R., (1991) Mol. Cell. Biol., 11, p. 1295; Wang, T., Bretscher, A., (1997) Genetics, 147, p. 1595; Chen, C.Y., Graham, T.R., (1998) Genetics, 150, p. 577; Mullen, J.R., Kaliraman, V., Ibrahim, S.S., Brill, S.J., (2001) Genetics, 157, p. 103; Herskowitz, I., Rine, J., Strathern, J., (1992) The molecular and cellular biology of the yeast saccharomyces cerevisiae, vol. 2, Gene Expression, 2, pp. 583-656. , E. W. Jones, J. R. Pringle, J. R. Broach, Eds. (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY); Kamei, T., (1998) J. Biol. Chem., 273, p. 28341; Evangelista, M., Nature Cell Biol.; Tjandra, H., Compton, J., Kellogg, D., (1998) Curr. Biol., 8, p. 991; Longtine, M.S., (2000) Mol. Cell. Biol., 20, p. 4049; Evangelista, H.M., (1997) Science, 276, p. 118; notenotenoteBader, G.D., (2001) Nucleic Acids Res., 29, p. 242. , www.bind.ca; http:vlado.fmf.uni-lj.si/pub/networks/paiekTong, A.H.Y., Science, , in preparation; noteWinter, D.C., Choe, E.Y., Li, R., (1999) Proc. Natl. Acad. Sci. U.S.A., 96, p. 7288; Cope, M.J., Yang, S., Shang, C., Drubin, D.G., (1999) J. Cell Biol, 144, p. 1203; Bloom, K., (2000) Nature Cell Biol., 2, pp. E96; Debrauwere, H., Loeillet, S., Lin, W., Lopes, J., Nicolas, A., (2001) Proc. Natl. Acad. Sci. U.S.A., 98, p. 8263; Kroll, E.S., Hyland, K.M., Hieter, P., Li, J.J., (1996) Genetics, 143, p. 95; noteHartwell, L.H., (1997) Science, 278, p. 1064; noteBarstead, R., (2001) Curr. Opin. Chem. Biol., 5, p. 63; Hughes, T.R., (2000) Nature Genet., 25, p. 333; Mochida, J., Yamamoto, T., Fujimura-Kamada, K., Tanaka, K., personal communicationShoemaker, D.D., Lashkari, D.A., Morris, D., Mittmann, M., Davis, R.W., (1996) Nature Genet., 14, p. 450. , wwwsequence.stanford.edu/group/yeast_deletion_project/deletions3.html; Maiolatesi, M., Bieganowski, P., Shoemaker, D., Brenner, C., personal communicationOoi, S.L., personal communicationnote","Andrews, B.; Department of Medical Genetics, University of Toronto, Toronto, Ont. M5S 1A8, Canada; email: brenda.andrews@utoronto.ca",,,,,,,,00368075,,SCIEA,10.1126/science.1065810,11743205,"English","Science",Article,Scopus
"Bader G.D., Donaldson I., Wolting C., Ouellette B.F.F., Pawson T., Hogue C.W.V.","BIND - The Biomolecular Interaction Network Database",2001,"Nucleic Acids Research",29,1,,242,245,,319,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0035171884&partnerID=40&md5=4aea202e18d48475fa5b9ee9956ecc17","Department of Biochemistry, University of Toronto, Toronto, Ont., Canada; Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; Centre for Molecular Medicine and Therapeutics, Children's and Women's Health Centre of British Columbia, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ont., Canada; Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada","Bader, G.D., Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; Donaldson, I., Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; Wolting, C., Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; Ouellette, B.F.F., Centre for Molecular Medicine and Therapeutics, Children's and Women's Health Centre of British Columbia, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Pawson, T., Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ont., Canada; Hogue, C.W.V., Department of Biochemistry, University of Toronto, Toronto, Ont., Canada, Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada, Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada","The Biomolecular Interaction Network Database (BIND; http://binddb.org) is a database designed to store full descriptions of interactions, molecular complexes and pathways. Development of the BIND 2.0 data model has led to the incorporation of virtually all components of molecular mechanisms including interactions between any two molecules composed of proteins, nucleic acids and small molecules. Chemical reactions, photochemical activation and conformational changes can also be described. Everything from small molecule biochemistry to signal transduction is abstracted in such a way that graph theory methods may be applied for data mining. The database can be used to study networks of interactions, to map pathways across taxonomic branches and to generate information for kinetic simulations. BIND anticipates the coming large influx of interaction information from high-throughput proteomics efforts including detailed information about post-translational modifications from mass spectrometry. Version 2.0 of the BIND data model is discussed as well as implementation, content and the open nature of the BIND project. The BIND data specification is available as ASN.1 and XML DTD.",,"nucleic acid; protein; proteome; article; biochemistry; chemical interaction; chemical reaction; conformational transition; controlled study; data base; kinetics; mass spectrometry; molecular interaction; photoactivation; priority journal; protein interaction; protein modification; protein processing; signal transduction; taxonomy; Binding, Competitive; Databases, Factual; DNA; Information Services; Internet; Kinetics; Models, Molecular; Protein Binding; Proteins",,"DNA, 9007-49-2; Proteins","Biomolecular Interaction Network Database",,,"Mendelsohn, A.R., Brent, R., Protein interaction methods-toward an endgame (1999) Science, 284, pp. 1948-1950; Cassman, M., Hunter, T., Pawson, T., Proteins suggest form of their own database (2000) Nature, 403, pp. 591-592; Pawson, T., Protein modules and signalling networks (1995) Nature, 373, pp. 573-580; Wheeler, D.L., Chappey, C., Lash, A.E., Leipe, D.D., Madden, T.L., Schuler, G.D., Tatusova, T.A., Rapp, B.A., Database resources of the National Center for Biotechnology Information (2001) Nucleic Acids Res., 29, pp. 11-16. , Updated article in this issue: Nucleic Acids Res. (2000), 28, 10-14; Ostell, J., Kans, J.A., (1998), 39, pp. 121-144. , Baxevanis,A.D. and Ouellette,B.F. (eds), Bioinformatics, A Practical Guide to the Analysis of Genes and Proteins. John Wiley and Sons, New York, NY(1996), Object Management Group CORBA Architecture and Specifications. OMG Publications, Needham, MAFenyo, D., The Biopolymer Markup Language (1999) Bioinformatics, 15, pp. 339-340; Bader, G.D., Hogue, C.W., BIND-a data specification for storing and describing biomolecular interactions, molecular complexes and pathways (2000) Bioinformatics, 16, pp. 465-477; Karp, P.D., An ontology for biological function based on molecular interactions (2000) Bioinformatics, 16, pp. 269-285; Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Eppig, J.T., Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium (2000) Nature Genet., 25, pp. 25-29; Hogue, C.W., Cn3D: A new generation of three-dimensional molecular structure viewer (1997) Trends Biochem. Sci., 22, pp. 314-316; Salcini, A.E., McGlade, J., Pelicci, G., Nicoletti, I., Pawson, T., Pelicci, P.G., Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins (1994) Oncogene, 9, pp. 2827-2836; Xenarios, I., Rice, D.W., Salwinski, L., Baron, M.K., Marcotte, E.M., Eisenberg, D., DIP: The database of interacting proteins (2001) Nucleic Acids Res., 29, pp. 239-241. , Updated article in this issue: Nucleic Acids Res. (2000), 28, 289-291; Uetz, P., Giot, L., Cagney, G., Mansfield, T.A., Judson, R.S., Knight, J.R., Lockshon, D., Pochart, P., A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae (2000) Nature, 403, pp. 623-627; Ito, T., Tashiro, K., Muta, S., Ozawa, R., Chiba, T., Nishizawa, M., Yamamoto, K., Sakaki, Y., Toward a protein-protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins (1997) Proc. Natl Acad. Sci. USA, 97, pp. 1143-1147; Marcotte, E.M., Pellegrini, M., Ng, H.L., Rice, D.W., Yeates, T.O., Eisenberg, D., Detecting protein function and protein-protein interactions from genome sequences (1999) Science, 285, pp. 751-753; Albert, R., Jeong, H., Barabasi, A.L., Error and attack tolerance of complex networks (2000) Nature, 406, pp. 378-382; Schaff, J., Loew, L.M., The virtual cell (1999) Pac. Symp. Biocomput., pp. 228-239","Hogue, C.W.V.; Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ont. M5G 1X5, Canada; email: hogue@mshri.on.ca",,,,,,,,03051048,,NARHA,,11125103,"English","Nucleic Acids Res.",Article,Scopus
"Bader G.D., Hogue C.W.V.","BIND - A data specification for storing and describing biomolecular interactions, molecular complexes and pathways",2000,"Bioinformatics",16,5,,465,477,,109,"http://www.scopus.com/inward/record.url?eid=2-s2.0-0033930882&partnerID=40&md5=18d2f22f5827f610215e946abeba244b","Department of Biochemistry, University of Toronto, Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada","Bader, G.D., Department of Biochemistry, University of Toronto, Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada; Hogue, C.W.V., Samuel Lunenfeld Research Institute, Toronto, Ont. M5G 1X5, Canada","Motivation: Proteomics is gearing up towards high-throughput methods for identifying and characterizing all of the proteins, protein domains and protein interactions in a cell and will eventually create more recorded biological information than the Human Genome Project. Each protein expressed in a cell can interact with various other proteins and molecules in the course of its function. A standard data specification is required that can describe and store this information in all its detail and allow efficient cross-platform transfer of data. A complete specification must be the basis for any database or tool for managing and analysing this information. Results: We have defined a complete data specification in ASN.1 that can describe information about biomolecular interactions, complexes and pathways. Our group is using this data specification in our database, the Biomolecular Interaction Network Database (BIND). An interaction record is based on the interaction between two objects. An object can be a protein, DNA, RNA, ligand, molecular complex or an interaction. Interaction description encompasses cellular location, experimental conditions used to observe the interaction, conserved sequence, molecular location, chemical action, kinetics, thermodynamics, and chemical state. Molecular complexes are defined as collections of more than two interactions that form a complex, with extra descriptive information such as complex topology. Pathways are defined as collections of more than two interactions that form a pathway, with additional descriptive information such as cell cycle stage. A request for proposal of a human readable flat-file format that mirrors the BIND data specification is also tendered for interested parties. Availability: The ASN.1 data specification for biomolecular interaction, molecular complex and pathway data is available at ftp://bioinfo.mshri. on.ca/pub/BIND/Spec/bind.asn. 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