Network analysis of protein-protein interactions relevant in atherosclerosis and rheumatoid arthritis
Ravisen Beemadoo, Anisah W. Ghoorah, Yasmina Jaufeerally‐Fakim · 2020
Atherosclerosis and rheumatoid arthritis are chronic inflammatory diseases of high incidence worldwide. Both diseases are driven by a complex pathogenesis involving molecular interactions between the myriad of genes or proteins which can be modeled as protein-protein interaction networks (PPIN). Here, we identify the common genes and their functional implications in pathways that underlie the common pathophysiology of RA and atherosclerosis using network analysis of PPIN. By integrating protein-protein interaction (PPI) data and gene-disease associations, we constructed a common PPIN to identify the common genes and their topological significance. We then performed network analysis to identify hub genes based on degree and betweenness centrality. Functional modules were identified and mapped to Gene Ontology (GO) annotations. The resulting PPIN consists of 1379 nodes and 1739 interactions with 26 hub genes representing the union of atherosclerosis and RA related genes. Of these 26 genes, PTGS2, VCAM-1, ICAM-1, TNF-α, ALOX5, TGFβ1 and FOS are identified as both hub and common inflammation genes. Five most significant functional modules are detected and GO analysis reveals that these genes are involved in inflammatory response, regulation of T cell proliferation and response to lipopolysaccharide as biological processes. Three significant pathways validated by KEGG are TNF, NFkB and Interleukin-17 signaling pathways. Dysregulation in both lipid metabolism and T cell differentiation and proliferation were found to be the main triggers causing an inflammatory response which was found to be the common shared pathology that links atherosclerosis and RA. These genes could represent potential biomarkers and drug targets for future research on RA and atherosclerosis and their associated comorbidities.