Protein-protein interaction networks: unraveling the wiring of molecular machines within the cell

Mapping and understanding of the protein interaction networks with their key modules and hubs can provide deeper insights into the molecular machinery underlying complex phenotypes. In this article, we present the basic characteristics and definitions of protein networks, starting with a distinction of the different types of associations between proteins. We focus the review on protein-protein interactions (PPIs), a subset of associations defined as physical contacts between proteins that occur by selective molecular docking in a particular biological context. We present such definition as opposed to other types of protein associations derived from regulatory, genetic, structural or functional relations. To determine PPIs, a variety of binary and co-complex methods exist; however, not all the technologies provide the same information and data quality. A way of increasing confidence in a given protein interaction is to integrate orthogonal experimental evidences. The use of several complementary methods testing each single interaction assesses the accuracy of PPI data and tries to minimize the occurrence of false interactions. Following this approach there have been important efforts to unify primary databases of experimentally proven PPIs into integrated databases. These meta-databases provide a measure of the confidence of interactions based on the number of experimental proofs that report them. As a conclusion, we can state that integrated information allows the building of more reliable interaction networks. Identification of communities, cliques, modules and hubs by analysing the topological parameters and graph properties of the protein networks allows the discovery of central/critical nodes, which are candidates to regulate cellular flux and dynamics.