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加权基因共表达网络分析识别出与冠状动脉疾病相关的特定模块和枢纽基因。

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

作者信息

Liu Jing, Jing Ling, Tu Xilin

机构信息

Department of Cardiology, Harbin the second hospital, Harbin, Heilongjiang, 150056, China.

Department of Cardiology, First affiliated hospital of Harbin medical university, Harbin, Heilongjiang, 150036, China.

出版信息

BMC Cardiovasc Disord. 2016 Mar 5;16:54. doi: 10.1186/s12872-016-0217-3.

Abstract

BACKGROUND

The 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.

METHODS

Microarray 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.

RESULTS

Total 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.

CONCLUSIONS

A 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.

摘要

背景

冠状动脉疾病(CAD)潜在分子靶点的分析对于理解疾病的分子机制至关重要。然而,CAD的全基因组芯片基因共表达分析研究仍然有限。

方法

从基因表达综合数据库下载CAD的芯片数据(GSE23561),包括CAD患者(n = 6)和对照组(n = 9)的外周血样本。使用R语言中的Limma软件包来识别CAD样本与对照样本之间的差异表达基因(DEG)。利用R语言中的加权基因共表达网络分析(WGCNA)软件包进行WGCNA分析,以识别网络中的显著模块。然后,使用DAVID软件对最显著模块中的基因进行功能和通路富集分析。此外,通过R语言中的isubpathwayminer软件包和GenCLiP 2.0工具对模块中的枢纽基因进行分析,以识别显著的子通路。

结果

在CAD样本中总共鉴定出3711个DEG及其21个模块。最显著的模块与肥厚型心肌病通路和膜相关功能有关。此外,选择了该模块中连接性高的前30个枢纽基因,并通过子通路筛选和数据挖掘将两个基因(G6PD和S100A7)作为关键分子。

结论

在CAD样本中检测到一个与肥厚型心肌病通路相关的模块。G6PD和S100A7是CAD的潜在靶点。我们的发现可能为CAD潜在的分子机制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2024/4779223/4291e42bdf6a/12872_2016_217_Fig1_HTML.jpg

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