Identification of key gene modules and hub genes associated with the fast development of Amyotrophic lateral sclerosis by weighted gene co-expression network analysis (WGCNA)

Background and Aim : Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is caused by degeneration and death of motor neurons in the brain and spinal cord. Weighted gene co-expression network analysis (WGCNA) is a novel and powerful method that detects gene interactions according to their co-expression similarities. In the present study, WGCNA was used to identify the gene modules and hub genes particularly correlated with the development of ALS in mouse models.Methods : A gene expression dataset was downloaded from the Gene Expression Omnibus (GEO) database and used WGCNA to dynamically study the changes of co-expression genes in the rapidly progressing mutant SOD1 mice models (129Sv-SOD1G93A) and the slowly progressing mutant SOD1 mice models (C57-SOD1G93A). Modules that highly correlated with ALS development, were carried out functional enrichment analysis for annotation, visualization, and integration discovery. Cytoscape software was used to construct a co-expression network and extracted the hub genes of modules. Differential gene expression analysis was done by the limma R package to obtain the expression level of hub genes.Results : Ten modules were detected in total and the brown module was extraordinarily correlated with ALS development (cor=0.97, P=1e 200). The top three functions of this module included: regulation of inflammatory response (P=1e 06), positive regulation of response to external stimulus (P=1e 06) and regulation of tumor necrosis factor production (P=1e-06). Cytoscape software identified the top four hub genes of the brown module that included: CLEC7A, CCL6, MPEG1 and AU020206. The expression levels of mentioned hub genes were significantly up-regulated in the rapidly progressing mutant SOD1 mice models compared to the slowly progressing mutant SOD1 mice models.Conclusion : The present study demonstrated that hub genes such as CLEC7A, CCL6, MPEG1 and AU020206 are highly correlated with the ALS development and may be used as new targets for the detection or treatment of ALS.

Keywords:

ALS development , WGCNA , Differential gene expression , hub genes