Predicting physiologically relevant SH3 domain mediated protein-protein interactions in yeast

Shobhit Jain and Gary Bader

Motivation

Many intracellular signaling processes are mediated by interactions involving peptide recognition modules such as SH3 domains. These domains bind to small, linear protein sequence motifs which can be identified using high-throughput experimental screens such as phage display. Binding motif patterns can then be used to computationally predict protein interactions mediated by these domains. While many protein-protein interaction prediction methods exist, most do not work with peptide recognition module mediated interactions or do not consider many of the known constraints governing physiologically relevant interactions between two proteins.

Results

A novel method for predicting physiologically relevant SH3 domain-peptide mediated protein-protein interactions in S. cerevisae using phage display data is presented. Like some previous similar methods, this method uses position weight matrix models of protein linear motif preference for individual SH3 domains to scan the proteome for potential hits and then filters these hits using a range of evidence sources related to sequence-based and cellular constraints on protein interactions. The novelty of this approach is the large number of evidence sources used and the method of combination of sequence based and protein pair based evidence sources. By combining different peptide and protein features using multiple Bayesian models we are able to predict high confidence interactions with an overall accuracy (F-score) between 0.98 and 0.96 across a range of interaction score thresholds.

Downloads

Latest Release

Source: DoMo-Pred.zip
Binary: DoMo-Pred-Binary.zip

Predictions

SH3_PPI_Predictions.zip

Text file format:

Domain

Peptide

Start

Stop

Sequence

Score

P11710

P53861

313

318

RTTSH

1.0

P11710

P32909

80

85

RTSSL

1.0

...

...

...

...

...

...

Supplementary material

supplementary.pdf

Software/DoMo-Pred (last edited 2015-07-24 03:51:10 by ShobhitJain)

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