Abstract
WD40 proteins are involved in a variety of protein-protein interactions as part of a multi-protein assembly modulating diverse and critical cellular process. It is known that several proteins of this family have been implicated in different disorders such as developmental abnormalities and cancer. However, molecular functions of many proteins in this family are yet unknown and it is of clinical interest. Therefore, it is of interest to define, construct, understand, analyze, evaluate, redefine and refine an interactome for WD40 protein family. We used data from literature mining using Cytoscape followed by linear regression analysis between Betweenness centrality and stress scores to define a model to filter the nodes in a representative WD40 interactome construction. We identified 10 ranked nodes in this analysis and subsequent microarray data selected three of them in insulin resistance that is further demonstrated in HepG2 cell culture models. We also observed the expression of GRWD1, RBBP5 and WDR5 genes during perturbation. Thus, we report hub nodes of WD40 interactome in insulin resistance. It should be noted that the pipeline using protein interaction network help find new proteins of clinical importance.