基于WGCNA分析探讨COVID-19相关心房颤动的关键途径

Analyzing the Key Pathways Associated with COVID-19-induced Atrial Fibrillation Using WGCNA

目的通过加权基因共表达网络分析(WGCNA)方法构建并分析COVID-19和心房颤动(房颤,AF)的共表达网络,探寻COVID-19相关AF可能发病机制。方法从GEO数据库(http://www.ncbi.nlm.nih.gov/geo/)中获得COVID-19和AF相关数据集,通过WGCNA识别疾病相关模块,将COVID-19和AF疾病相关模块中的基因进行交叉,得到COVID-19相关AF的共享基因,进行GO、KEGG、Reactome、WIKI Pathway分析探寻可能的生物学功能,并构建PPI蛋白网络互作图,运用Cytoscape软件确定关键基因和关键通路。结果共得到45个COVID-19和AF的共享基因,富集分析显示目标基因涉及多个生物学进程及通路,其中MAPK信号通路最值得关注。结论探讨了COVID-19和AF之间联系的分子机制,得到了3个关键基因MAP3K1、CREB1、RPS6KA3,认为AngⅡ-MAPK信号通路的过度激活所导致的炎症风暴在COVID-19相关AF中发挥了关键作用。

Objective To construct and analyze the co-expression network of COVID-19 and atrial fibrillation(AF)by weighted gene co-expression network analysis(WGCNA)method,to explore the possible pathogenesis of COVID-19-related atrial fibrillation;Methods Obtain COVID-19 and atrial fibrillation-related datasets from the GEO database(http://www.ncbi.nlm.nih.gov/geo/),identify disease-related modules through WGCNA,and integrate COVID-19 and AF disease-related modules into The genes were crossed to obtain the shared genes of COVID-19-related AF,conduct GO,KEGG,Reactome,WIKI Pathway analysis to explore possible biological functions,construct PPI protein network interaction map,and use Cytoscape software to determine key genes and key pathways;Results A total of 45 shared genes between COVID-19 and AF were obtained,and the enrichment analysis showed that the target genes were involved in multiple biological processes and pathways,among which the MAPK signaling pathway was the most noteworthy;Conclusion We have explored the molecular mechanisms linking COVID-19 and AF,and identified three key genes:MAP3K1,CREB1,and RPS6KA3.We suggest that the excessive activation of the AngⅡ-MAPK signaling pathway leading to an inflammatory storm plays a key role in COVID-19-associated AF.