Network topology analysis of essential genes interactome of Helicobacter pylori to explore novel therapeutic targets

Abstract

The Helicobacter pylori chronic colonization produces a wide range of gastric diseases in the gastric mucosa by abetting inflammation. Amidst coevolution and reorganization of its metabolism with humans, it has become difficult still imperative to understand and prevent its growth. This study focus to explore functional insights into identification of hub proteins/genes by aggregating the behavior of genes connected in a protein-protein interaction (PPI) network. We have constructed a PPI network of 123 essential genes along with 1213 interactions in H. pylori 26695. The degree and other centrality measures analysis assist in identifying the important hub nodes, which are top-ranked proteins. A total of nine proteins (recA, guaA, dnaK, rpsB, rplQ, rpmA, rpmC, rpmF, and rpsE) were obtained with high degree (k), betweenness centrality (BC) value. Gene ontology analysis reveals 8, 5 and 3 GO terms correspond to biological processes, cellular components and molecular function respectively. Gene complexes of hypothetical proteins (HPs) were related to aminoacyl-tRNA biosynthesis, biosynthesis of secondary metabolites, bacterial secretion system and protein export. The MCODE analysis revealed that protein from module M1, M3 and M6 include the proteins which have highest degree and BC values. It is noteworthy to mention that the bifunctional GMP synthase/glutamine amidotransferase protein (guaA), molecular chaperon (dnaK), recombinase A (recA) constitute as hub proteins. As a result, these genes are considered as network hub nodes that might be used as therapeutic targets. Our analysis affords a detailed understanding of the molecular process and pathways regulated by the essential genes in H. pylori 26695.