Evaluation of nonsynonymous single nucleotide variations in NOS2 Gene identified through whole exome sequencing: A bioinformatics approach

Majority of the human diseases are accounted for by nonsynonymous single nucleotide variations (nsSNVs) that occur in the coding region of genes and alter the amino acid residues at specific positions. The future of genomics research is in identification of nsSNVs that contribute to disease pathophysiology by disrupting protein function. A robust pipeline with several integrated computational prediction tools facilitates prioritization of significant disease- associated nsSNVs. In this study, we analysed 30 rare frequency missense variations in NOS2 identified through Whole Exome Sequencing (WES) of six coronary artery disease (CAD) using multiple bioinformatics softwares and tools. We employed a stringent filtering workflow to identify and assess the pathogenic effect of nsSNVs on NOS2 structure and function. We used a combination of deleterious variation detection tools, protein stability changes prediction, post-translational modification site prediction, protein-protein interaction and enrichment analyses to discern disease-associated variations. Our findings implicate four amino acid substitutions - K730N, P769R, P958S and L1012S as candidates in pathological process of NOS2.