Abstract

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 of 0.97.Availability and implementation: Domain-Motif Mediated Interaction Prediction (DoMo-Pred) command line tool and all relevant datasets are available under GNU LGPL license for download from http://www.baderlab.org/Software/DoMo-Pred. The DoMo-Pred command line tool is implemented using Python 2.7 and C ++.Contact: gary.bader@utoronto.caSupplementary information: Supplementary data are available at Bioinformatics online.

Highlights

  • Protein–protein interactions (PPIs) are physical associations between protein pairs in a specific biological context

  • We focus on interactions involving peptide recognition modules (PRMs), in particular Src homology three (SH3), which are important in many cellular signaling processes

  • Gene expression data alone is not as powerful as others in discriminating positives from negatives (Kim et al, 2014), which may be due to its moderate correlation with protein expression (Vogel and Marcotte, 2012)

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Summary

Introduction

Protein–protein interactions (PPIs) are physical associations between protein pairs in a specific biological context. Their knowledge provides important insights into the functioning of a cell. Though the detected PPIs are largely accurate, these techniques are difficult to apply to whole proteome analysis. Genome-scale methods are highly resource intensive and single projects and techniques do not cover all known protein interactions. They only cover interactions in one organism at a time.

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