Comparative analysis of Pure Hubs and Pure Bottlenecks in Human Protein-protein Interaction Networks

Abstract

Bottlenecks and hubs form a set of topologically important nodes in a network. In this communication, we have made a detailed investigation on hubs and bottlenecks in human protein-protein interaction networks. We find that, three distinct groups exist which we refer to as: a) pure hubs (PHs, nodes having high degree but low betweenness values), b) mix proteins (MXs, nodes having both high degree and high betweenness values) and c) pure bottlenecks (PBs, nodes having high betweenness values but low degree values). Our investigations have revealed that pure hubs, as compared with MXs and PBs, (i) are more disordered, (ii) have higher potential to bind to multiple partners, (iii) are enriched with essential proteins as well as enriched with a higher number of splice variants. The MX proteins, as compared with PHs and PBs, (i) show slower evolutionary patterns, (ii) are involved in multiple pathways, (iii) enriched with the products of genes associated with various diseases and (iv) are more often targeted by bacteria, viruses, protozoa, and fungi pathogens. PBs, as compared with the PHs and MXs, (i) are associated with cancer genes and (ii) are the targets or the nearest neighbors of the targets of most of the approved drugs. Furthermore, our study revealed that these three categories of proteins are involved in distinct functional roles; PHs are involved in housekeeping processes such as transcription and replication; MXs proteins are involved in core signaling pathways whereas PBs are involved in signal transduction processes. Our work, therefore, has identified the distinct characteristics features associated with pure hubs, mix proteins and pure bottlenecks and thus helps in prioritizing proteins based on their degree and betweenness centrality values.