Protein-Interaction-Networks: More than mere modules

TL;DR

This paper challenges the traditional view of modules in protein-interaction networks, proposing a novel network decomposition into functional roles that better captures biological structure and function.

Contribution

It introduces a new method for decomposing protein-interaction networks into functional roles, surpassing the traditional module-based approach.

Findings

Traditional modules miss important network structures

Functional role decomposition captures network function more effectively

Impacts protein function prediction methods

Abstract

Cellular function is widely believed to be organized in a modular fashion. On all scales and at all levels of complexity, relatively independent sub-units perform relatively independent sub-tasks of biological function. This functional modularity must be reflected in the topology of molecular networks. But how a functional module should be represented in an interaction network is an open question. In protein-interaction networks (PIN), one can identify a protein-complex as a module on a small scale, i.e. modules are understood as densely linked, resp. interacting, groups of proteins, that are only sparsely interacting with the rest of the network. In this contribution, we show that extrapolating this concept of cohesively linked clusters of proteins as modules to the scale of the entire PIN inevitable misses important and functionally relevant structure inherent in the network. As an alternative, we introduce a novel way of decomposing a network into functional roles and show that this represents network structure and function more efficiently. This finding should have a profound impact on all module assisted methods of protein function prediction and should shed new light on how functional modules can be represented in molecular interaction networks in general.