Uncovering potential Drug Targets for Tuberculosis using Protein Networks.

Abstract

The emergence of HIV-TB co-infection and multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) drive the need for new therapeutics against the infectious disease tuberculosis. Among the reported putative TB targets in the literature, the identification and characterization of the most probable therapeutic targets that influence the complex infectious disease, primarily through interactions with other influenced proteins, remains a statistical and computational challenge in proteomic epidemiology. Protein interaction network analysis provides an effective way to understand the relationships between protein products of genes by interconnecting networks of essential genes and its protein-protein interactions for 5 broad functional categories in Mtb. We also investigated the substructure of the protein interaction network and focused on highly connected nodes known as cliques by giving weight to the edges using data mining algorithms. Cliques containing Sulphate assimilation and Shikimate pathway enzymes appeared continuously inspite of increasing constraints applied by the K-Core algorithm during Network Decomposition. The potential target narrowed down through Systems approaches was Prephanate Dehydratase present in the Shikimate pathway this gives an insight to develop novel potential inhibitors through Structure Based Drug Design with natural compounds.