基于加权基因共表达网络分析鉴定心房颤动发病的关键基因

Identification of hub genes in the pathogenesis of atrial fibrillation based on weighted gene co-expression network analysis

目的鉴定房颤(AF)发病机制中的关键基因(Hub Gene)。方法从GEO数据库中下载GSE161450作为训练集筛选差异表达基因,并通过系统加权基因共表达网络分析(WGCNA)寻找与AF相关的模块和候选基因。将差异表达基因与WGCNA中的性状模块基因取交集,获取Hub Gene,而后对Hub Gene进行基因功能注解(GO)和蛋白质-蛋白质相互作用(PPI)分析。结果共构建8个具有强保守性模块,其中MEbrown模块与AF显著相关,并鉴定出5个Hub Gene,分别为:超极化激活环状核苷酸门控通道2(HCN2)、亲离子型谷氨酸受体5(GRIK5)、乙酰胆碱受体E(CHRNE)、钾向内整流通道亚族J成员2(KCNJ2)和热休克蛋白家族成员2(HSPA2)。此Hub Gene主要聚集于GO:0034702离子通道复合体(ion channel complex),GO:1902495跨膜转运体复合体(transmembrane transporter complex)和GO:1990351转运体复合体(transporter complex)三个通路。结论WGCNA分析鉴定出与AF发病相关的5个Hub Gene可能有助于AF发病机制的阐述。

Objective To identify hub genes involved in the pathogenesis of atrial fibrillation(AF).Methods GSE161450 was downloaded from the GEO database as a training set to screen for differentially expressed genes,and systematic weighted gene co-expression network analysis(WGCNA)was used to identify AF-related modules and candidate genes.The differentially expressed genes were intersected with the trait module genes in WGCNA to obtain the hub gene,and the hub gene was then subjected to gene function annotation(GO)and protein-protein interaction(PPI)analysis.Results A total of 8 modules with strong conservatism were constructed,among which the MEbrown module was significantly correlated with AF,and 5 Hub Genes were identified,namely:hyperpolarization-activated cyclic nucleotide-gated channel 2(HCN2),ionotropic glutamate receptor 5(GRIK5),acetylcholine receptor E(CHRNE),potassium inward rectifier channel subfamily J member 2(KCNJ2),and heat shock protein family member 2(HSPA2).This hub gene cluster is concentrated in three pathways,GO:0034702 ion channel complex,GO:1902495 transmembrane transporter complex,and GO:1990351 transporter complex.Conclusion WGCNA analysis identified 5 Hub Genes related to the pathogenesis of AF,which may contribute to the elucidation of the pathogenesis of AF.