Construction and contextualization approaches for protein-protein interaction networks.

Protein-protein interaction network (PPIN) analysis is a widely used method to study the contextual role of proteins of interest, to predict novel disease genes, disease or functional modules, and to identify novel drug targets. PPIN-based analysis uses both generic and context-specific networks. Multiple contextualization methodologies have been described, such as shortest-path algorithms, neighborhood-based methods, and diffusion/propagation algorithms. This review discusses these methods, provides intuitive representations of PPIN contextualization, and also examines how the quality of such context-specific networks could be improved by considering additional sources of evidence. As a heuristic, we observe that tasks such as identifying disease genes, drug targets, and protein complexes should consider local neighborhoods, while uncovering disease mechanisms and discovering disease-pathways would gain from diffusion-based construction.