Uncovering disease mechanisms through network biology in the era of Next Generation Sequencing

• DOI: 10.1038/srep24570
• Publication Date: 2016-04-15T09:31:29Z
• Authors: Janet Piñero; Ariel Berenstein; Abel Gonzalez-Perez; Ariel Chernomoretz; Laura I. Furlong
• Keywords: Interactome; Gene regulatory network; Exome; Interaction network

Abstract Characterizing the behavior of disease genes in context biological networks has potential to shed light on mechanisms, and reveal both new candidate therapeutic targets. Previous studies addressing network properties have produced contradictory results. Here we explored causes these discrepancies assessed relationship between roles their tolerance deleterious germline variants human populations leveraging on: abundance interactome resources, a comprehensive catalog exome variation data. We found that most salient features are driven by cancer related different types diseases play whose centrality is inversely correlated likely mutations. This proved be multiscale signature, including global, mesoscopic local features. Cancer driver genes, sensitive variants, occupy central positions, followed dominant then recessive which tolerant isolated within modules.