Identifying key modules and genes associated with Focal andSegmental Glomerulosclerosis Pathogenesis using an integrated WGCNA and PPI network analysis

Focal segmental glomerulosclerosis (FSGS) is a heterogeneous renal histopathological disorder that is highly prevalent globally and primarily a↵ects the glomerulus. Despite extensive research, the molecular basis of focal and segmental glomerulosclerosis (FSGS) is yet to be elucidated. This study aimed to analyze an FSGS-related microarray dataset (GSE۱۰۸۱۰۹) from the Gene Expression Omnibus database in order to uncover the top pathways and molecules involved in the pathogenesis of this disorder. After quality checking, normalization, and analysis of the dataset, a protein-protein interaction network was constructed using ۳۳۱۵ significant di↵erentially expressed genes (DEGs) . Hub molecules were identified in the network based on their degree of centrality. WGCNA was used to group di↵erentially expressed genes (DEGs) into nine co-expression modules . hub molecules were selected based on module membership and gene significance values. The turquoise module, which was most correlated to the disease, was then chosen for further enrichment analysis. Gene ontology and Reactome pathway enrichment analyses revealed that Th۱۷ cell differentiation, Apoptosis, B cell receptor signaling pathway, Th۱ and Th۲ cell di↵erentiation, and Fc gamma R-mediated phagocytosis were among the top enriched terms for the turquoise module’s DEGs . Nine hub molecules including CD۳۴, ITGA۵, TGFB۱, GATA۳, GNAI۲, CYBB, LYN, NOTCH۱, and CDH۵ were identified as primary molecules shared between the two methods. These nine molecules and associated pathways have been proposed as potentially contributory to the pathogenesis of FSGS.

کلیدواژه ها:

Glomerulosclerosis ، Segmental glomerulosclerosis ، Weighted gene co-expression network ، Drug target