Identifying the immunodeficiency gateway proteins in humans and their involvement in microRNA regulation

Abstract

Very little is known to date about the regulation protocol between transcription factors (TFs), genes and microRNAs (miRNAs) associated with diseases in various organisms. In this paper, we focus on finding the activity of miRNAs through the HIV-1 regulatory pathway in humans at the systems level. For this, we integrate and study the characteristics of the interaction information between HIV-1 and human proteins obtained from literature and prediction analysis. This information, realized in the form of a bipartite network, is subsequently mined with an exhaustive graph search technique to identify the strong significant biclusters, which are effectively the bicliques. They are unified further to form the core bipartite subnetwork. Many of the known HIV-1 associated kinase proteins (including LCK) are found in this core module. From this, the secondary significant proteins are identified by mapping these gateway proteins to the human protein–protein interaction network. Finally, these proteins are mapped onto the TF-to-miRNA and miRNA-to-gene regulatory networks derived from a couple of current studies to obtain a global view of the HIV-1 mediated TF-gene-miRNA inter-regulatory network. Interestingly, a few miRNAs participating in this pathway at the secondary level are found to have oncogenic involvement.