Weighted gene co-expression network analysis to define pivotal modules and genes in diabetic heart failure

Abstract

Abstract This research was carried out to reveal specific hub genes involved in diabetic heart failure, as well as remarkable pathways that hub genes locate. The GSE26887 dataset from the GEO website was downloaded. The gene co-expression network was generated and central modules were analyzed to identify key genes using the WGCNA method. Functional analyses were conducted on genes of the clinical interest modules via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) enrichment, associated with protein–protein interaction (PPI) network construction in a sequence. Centrality parameters of the PPI network were determined using the CentiScape plugin in Cytoscape. Key genes, defined as genes in the ≥95% percentile of the degree distribution of significantly perturbed networks, were identified. Twenty gene co-expression modules were detected by WGCNA analysis. The module marked in light yellow exhibited the most significant association with diabetes (P=0.08). Genes involved in this module were primarily located in immune response, plasma membrane and receptor binding, as shown by the GO analysis. These genes were primarily assembled in endocytosis and phagosomes for KEGG pathway enrichment. Three key genes, STK39, HLA-DPB1 and RAB5C, which may be key genes for diabetic heart failure, were identified. To our knowledge, our study is the first to have constructed the co-expression network involved in diabetic heart failure using the WGCNA method. The results of the present study have provided better understanding the molecular mechanism of diabetic heart failure.