BRAIN Project

The Biologically Relevant Analysis of Interaction Networks (BRAIN) is a set of algorithms for predicting and analyzing protein domain-peptide ligand interactions based on experimentally known binding evidence (e.g. from protein chip or phage display experiments).

BRAIN can be accessed as a Cytoscape plugin which reads peptide binding profiles and generates interactions displayed as a Cytoscape network.

BRAIN consists of a library or API, and of a Cytoscape plugin.

BRAIN Library

The BRAIN library holds the algorithms and methods for interaction prediction. This library is required to build the BRAIN plugin.

BRAIN Plugin

The BRAIN plugin is a way of running various BRAIN algorithms from the Cytoscape user interface. The plugin runs a prediction analysis and presents the results visually as an interactive Cytoscape network.

Downloads

The BRAIN library and plugin are available below for download as Java archive (JAR) files and Java source tree tarballs.

Latest Release

BRAIN Plugin: Version 1.0.5 alpha (May 23, 2007)
Build: brainPlugin.jar
Source: BRAIN-Plugin-1.0.5-src.tgz

BRAIN Library: Version 1.4 (September 29, 2008)
Build: brainlib-1.4.jar
Source: To be posted by October 3, 2008

Dependencies: Additional JARs required by BRAIN - brainDeps.tar.gz

Earlier Releases

BRAIN Library: Version 1.3 (May 12, 2008)
Build: brainlib-1.3.jar
Source: BRAIN-Library-1.3-src.tgz

Installing the Plugin

System Requirements

• Java Runtime Environment (JRE) 1.5 or later

• Cytoscape 2.4.1 or later

Installation

• Place brainPlugin.jar and brainlib_1.1.jar in the Cytoscape plugins directory (located in the Cytoscape program directory, e.g. /usr/local/bin/Cytoscape or C:\Program Files\Cytoscape_v2.4.1)

• Extract and place all files from brainDeps.tar.gz into the Cytoscape lib directory (located in the Cytoscape program directory)

• Launch Cytoscape

• Look in the Plugins menu for the BRAIN item. If you don't see it there, revisit the above steps to make sure all files are in the right place.

Running the Plugin

• Launch Cytoscape

• Set analysis parameters from Plugins > BRAIN > Set Parameters

• Start the BRAIN analysis from Plugins > BRAIN > Run BRAIN

Notes on Using BRAIN

BRAIN takes one or more query proteins and their respective peptide ligands, builds a PWM-based profile for each protein, searches a protein sequence database for similar profiles, and returns a ranked set of proteins that are predicted to interact with the query proteins.

A query protein and its experimentally determined peptide ligands are represented as a peptide file, in which the peptide binders are listed as an ungapped multiple sequence alignment. The plugin can open a single peptide file, or multiple peptide files that are grouped into a project file. From a peptide file, BRAIN generates a position weight matrix (PWM), or protein profile. The profile constitutes the distributions of amino acids (rows) at each of the positions (columns) of the peptide pattern. In a given column of the PWM, each amino acid is assigned a weight based on its frequency of occurrence at the given position. These weights are normalized to 1.0 to emulate probabilities of occurrence.

BRAIN searches a protein sequence database (in FASTA, SwissProt, GenPept, or EMBL format) for the pattern represented by the protein profile. An interaction score (p-value) is calculated for each hit, and all hits exceeding the user-provided score threshold are reported as predicted interactors of the query protein. The output is provided as a Cytoscape network, enabling further graph-based analysis and exploration of node (protein) and edge (interaction) attributes including interaction score, gene name, motif sequence, and associated OMIM or MorbidMap record (if available).

Release Notes

BRAIN Library 1.4 (September 29, 2008)

• Supports the Cytoscape Task API to display a progress bar during logo tree generation

BRAIN Library 1.3 (May 12, 2008)

• Single linkage hierarchical clustering used to cluster profiles for generating logo tree
• Sequence logo alignment algorithm added for generating logo trees
• New code for amino acid grouping and coloring schemes to be defined, e.g. for generating sequence logos and logo trees

BRAIN Library 1.2 (February 2008)

• Internal release for alpha-testing

BRAIN Library 1.1 (July 26, 2007)

• Added PDZ symbol style for PDZ type residue colouring in sequence logo generation code (required by LoLA tool)

1.0.6 (June 12, 2007)

• brain.jar: Ability to retrieve additional database references from ProteinProfile object (previously was only able to retrieve the first ID in the Accession field of the peptide file).

1.0.5 (May 23, 2007)

• Code reorganization: brainPlugin.jar now holds only those classes related to the Cytoscape plugin. All other code has been moved to a new Brain Library project.

1.0.4 (May 15, 2007)

• Network node can represent a single domain or a protein containing multiple domain instances (via new Advanced Options tab)
• Lower scoring motif hits are now reported

• New node attribute Domain Name to hold a semantic domain identifier (Gene Name + Domain Number, for now)

1.0.3 (April 23, 2007)

• Support for new peptide file format version 1.1 (and back-compatible with format version 1.0)

• New node attributes Sequence Start, Sequence Stop, Comment for profiles generated from new peptide file format

1.0.2 (April 11, 2007)

• Report SNPs for entire protein sequence and for domain subsequence only.
• Option to specify codon bias file
• Option to load unique peptides only from peptide file(s)

1.0.1 (February 21, 2007)

• Port to Cytoscape API 2.4 and Java SE 5.0

Future Developments

(in order of priority)

1. Regular expression filtering of profile search results.
2. Expose auto-score threshold functionality in Profile Search panel (allow the user to specify automatic score threshold setting instead of having to specify a score threshold themselves).
3. Expose "regex" search features - new Pattern Search panel similar to Profile Search
4. New feature: consider aa groups in PWM searching
5. Design an improved scoring scheme (e.g. take into account surface accessibility) and drop down box to select different scores.

Contact

If you have any questions or feedback, please email Moyez Dharsee at mdharsee@infochromics.com.