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加权基因共表达网络分析鉴定干燥综合征关键基因及通路
作者:任田1  莫明兴2  曾克勤1  周二叶1  武剑1 
单位:1. 苏州大学附属第一医院 风湿科, 江苏 苏州 215006;
2. 苏州大学附属独墅湖医院 信息科, 江苏 苏州 215006
关键词:干燥综合征 生物信息学 共表达网络 基因 
分类号:R593
出版年·卷·期(页码):2023·51·第九期(1246-1251)
摘要:

目的:通过生物信息学方法探索干燥综合征(SS)关键基因及通路。方法: 从GEO数据库下载SS患者基因芯片数据,通过加权基因共表达网络分析(WGCNA),筛选出与临床信息相关性最高的核心模块,将核心模块内基因导入STRING数据库构建蛋白互作网络,并采用Cytoscape软件筛选出核心基因并在GeneMANIA中进行功能分析及验证。结果:通过WGCNA共筛选出14个模块,其中MEyellow模块与临床相关性最高作为核心模块。采用Cytoscape软件筛选出连接度最高的前5位基因IFIT1、IFIT3、MX1、RSAD2、XAF1作为关键基因,GeneMANIA功能分析显示5个关键基因及其相关联基因主要参与Ⅰ型干扰素信号通路、病毒应答通路。在数据集GSE51092中,关键基因IFIT1、IFIT3、MX1、RSAD2、XAF1表达水平均明显高于健康对照组(P<0.01),且受试者工作特征(ROC)曲线表明,关键基因IFIT1、IFIT3、RSAD2、XAF1均可区分SS患者与健康人群[均曲线下面积(AUC)>0.85,P<0.01]。结论:通过生物信息学分析鉴定IFIT1、IFIT3、MX1、RSAD2、XAF1可能是与SS相关的关键基因,为探究SS的发病机制提供了理论依据与新的方向。

Objective: To identify the key genes and functionally enriched pathways of sjgren's syndrome(SS)by bioinformatics analysis.Methods: We downloaded the microarray datas of SS from Gene Expression Omnibus(GEO).Gene network was constructed and genes were classified into different modules using the weighted gene co-expression network analysis(WGCNA). Function enrichment analysis of the hub module most associated with SS was performed. The genes in the hub module were imported into the STRING database,the protein-protein interaction network was constructed,then the hub genes were screened by Cytoscape software,verified and analyzed function by GeneMANIA.Results: Genes were classified into 14 modules using WGCNA.Among them,the ME yellow module was most closely associated with SS.The top five hub genes with the highest connectivity were IFIT1,IFIT3,MX1,RSAD2 and XAF1 screened by Cytoscape software.These genes were significantly enriched in regulation of type I interferon production and response to virus.The expression levels of the five key genes were confirmed in dataset GSE51092.Receiver operating characteristic(ROC) curve analysis determined that IFIT1,IFIT3,RSAD2,XAF1expression can distinguish SS from controls with all area under curve(AUC) more than 0.85,P<0.01. Conclusion: Bioinformatics analysis shows that IFIT1, IFIT3, MX1, RSAD2, XAF1 may be the pivot genes related to SS,which provides a theoretical basis and a new direction for the pathogenesis research of SS.

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