Weighted gene co-expression network analysis identifies specific modules and hub genes related to coronary artery disease.

Jing Liu,Ling Jing,Xilin Tu

doi:10.1186/s12872-016-0217-3

Abstract

BackgroundThe analysis of the potential molecule targets of coronary artery disease (CAD) is critical for understanding the molecular mechanisms of disease. However, studies of global microarray gene co-expression analysis of CAD still remain limited.MethodsMicroarray data of CAD (GSE23561) were downloaded from Gene Expression Omnibus, including peripheral blood samples from CAD patients (n = 6) and controls (n = 9). Limma package in R was used to identify the differentially expressed genes (DEGs) between CAD and control samples. Using weighted gene co-expression network analysis (WGCNA) package in R, WGCNA was performed to identify significant modules in the network. Then, functional and pathway enrichment analyses were conducted for genes in the most significant module using DAVID software. Moreover, hub genes in the module were analyzed by isubpathwayminer package in R and GenCLiP 2.0 tool to identify the significant sub-pathways.ResultsTotal 3711 DEGs and 21 modules for them were identified in CAD samples. The most significant module was associated with the pathways of hypertrophic cardiomyopathy and membrane related functions. In addition, the top 30 hub genes with high connectivity in the module were selected, and two genes (G6PD and S100A7) were taken as key molecules via sub-pathway screening and data mining.ConclusionsA module associated with hypertrophic cardiomyopathy pathway was detected in CAD samples. G6PD and S100A7 were the potential targets in CAD. Our finding might provide novel insight into the underlying molecular mechanism of CAD.

Highlights

The analysis of the potential molecule targets of coronary artery disease (CAD) is critical for understanding the molecular mechanisms of disease
Microarray data Microarray data of GSE23561 [16] was downloaded from the National Center For Biotechnology Information (NCBI) Gene Expression Omnibus (GEO, http:// www.ncbi.nlm.nih.gov/geo/) database [17, 18], which was based on the platform of GPL10775 Human 50 K Exonic Evidence-Based Oligonucleotide Array
Data preprocessing and differentially expressed genes (DEGs) screening After data preprocessing, the expression matrices of 24277 genes were obtained from the 15 samples

Summary

Introduction

The analysis of the potential molecule targets of coronary artery disease (CAD) is critical for understanding the molecular mechanisms of disease. Studies of global microarray gene co-expression analysis of CAD still remain limited. Coronary artery disease (CAD, named ischemic heart disease, atherosclerotic cardiovascular disease, atherosclerotic heart disease and coronary heart disease) is one of the most common forms of heart disease that remains a leading cause of morbidity and mortality in the entire world population [1, 2]. Plenty of genetic changes in CAD have been identified, increasing our understanding to the underlying molecular mechanism of CAD. Lipase (LIPA) gene is proved to be associated with prevalent cardiovascular risk factors for CAD [7].

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