Identification of Key Causal Regulators in Gene Networks

One primary goal of gene network analysis is to identify key regulatory components, or key drivers, of sub-networks with respect to various biological contexts. Here we developed a general algorithm to identify key drivers in gene regulatory networks. The generalized key driver analysis (KDA) uncovers not only the well-known regulators for the expression quantitative trait locus (eQTL) hotspots but also many novel drivers underlying certain eQTL hotspots. This algorithm also identifies a number of key regulators for immune response involved in multiple common chronic diseases and the predicted drivers appear to be more important than the non-drivers genes to induce phenotypic changes when perturbed.