Abstract

BackgroundIn recent years, a considerable amount of research effort has been directed to the analysis of biological networks with the availability of genome-scale networks of genes and/or proteins of an increasing number of organisms. A protein-protein interaction (PPI) network is a particular biological network which represents physical interactions between pairs of proteins of an organism. Major research on PPI networks has focused on understanding the topological organization of PPI networks, evolution of PPI networks and identification of conserved subnetworks across different species, discovery of modules of interaction, use of PPI networks for functional annotation of uncharacterized proteins, and improvement of the accuracy of currently available networks.ResultsIn this article, we map known functional annotations of proteins onto a PPI network in order to identify frequently occurring interaction patterns in the functional space. We propose a new frequent pattern identification technique, PPISpan, adapted specifically for PPI networks from a well-known frequent subgraph identification method, gSpan. Existing module discovery techniques either look for specific clique-like highly interacting protein clusters or linear paths of interaction. However, our goal is different; instead of single clusters or pathways, we look for recurring functional interaction patterns in arbitrary topologies. We have applied PPISpan on PPI networks of Saccharomyces cerevisiae and identified a number of frequently occurring functional interaction patterns.ConclusionWith the help of PPISpan, recurring functional interaction patterns in an organism's PPI network can be identified. Such an analysis offers a new perspective on the modular organization of PPI networks. The complete list of identified functional interaction patterns is available at .

Highlights

  • In recent years, a considerable amount of research effort has been directed to the analysis of biological networks with the availability of genome-scale networks of genes and/or proteins of an increasing number of organisms

  • We searched for patterns on three of the protein-protein interaction (PPI) networks of Saccharomyces cerevisiae available in public databases: 1) Database of Interacting Proteins (DIP) database which contains experimentally determined interactions [46], 2) STRING database which provides confidence weighted predicted interactions using multiple data sources, and 3) WI-PHI database which provides confidence weighted predicted interactions enriched for physical interactions

  • We labeled the nodes of the PPI network using the available Gene Ontology (GO) Slim molecular functional annotations for yeast proteins

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Summary

Introduction

A considerable amount of research effort has been directed to the analysis of biological networks with the availability of genome-scale networks of genes and/or proteins of an increasing number of organisms. In parallel with the availability of genome-scale protein networks, various studies have been conducted to analyze these networks in order to understand their topological organization [8,9,10], identify conserved subnetworks across different species [11,12], discover modules of interaction [13,14,15,16,17,18], predict functions of uncharacterized proteins [19,20,21], and improve the accuracy of currently available networks [5,22,23,24,25,26]. Our work can be thought of as an adaptation of Alon's work on gene regulatory patterns to protein-protein interaction patterns

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