The Function of Communities in Protein Interaction Networks at Multiple Scales

TL;DR

This study explores how the scale of analysis affects the functional coherence of communities in yeast protein interaction networks, revealing that most proteins belong to functionally homogeneous communities at some scale.

Contribution

The paper introduces a novel method to assess functional homogeneity of network communities across multiple scales in protein interaction networks.

Findings

Functional homogeneity varies with network scale.

Almost all proteins are in a functionally homogeneous community at some scale.

High clustering coefficient correlates with functional homogeneity.

Abstract

Background: If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. Results: Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein. Conclusions: We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.