Genome-scale protein interaction network construction and topology analysis of functional hypothetical proteins in Helicobacter pylori divulges novel therapeutic targets

The emergence and spread of multi-drug resistance among Helicobacter pylori (H. pylori) strain raise more stakes for genetic research for discovering new drugs. The quantity of uncharacterized hypothetical proteins in the genome may provide an opportunity to explore their property and promulgation could act as a platform for designing the drugs, making them an intriguing genetic target. In this context, the present study aims to identify the key hypothetical proteins (HPs) and their biological regulatory processes in H. pylori. This investigation could provide a foundation to establish the molecular connectivity among the pathways using topological analysis of the protein interaction networks (PINs). The giant network derived from the extended network has 374 nodes connected via 925 edges. A total of 43 proteins with high betweenness centrality (BC), 54 proteins with a large degree, and 23 proteins with high BC and large degrees have been identified. HP 1479, HP 0056, HP 1481, HP 1021, HP 0043, HP 1019, gmd, flgA, HP 0472, HP 1486, HP 1478, and HP 1473 are categorized as hub nodes because they have a higher number of direct connections and are potentially more important in understanding HP's molecular interactions. The pathway enrichment analysis of the network clusters revealed significant involvement of HPs in pathways such as flagellar assembly, bacterial chemotaxis and lipopolysaccharide biosynthesis. This comprehensive computational study revealed HP's functional role and its druggability characteristics, which could be useful in the development of drugs to combat H. pylori infections.