基于加权基因共表达网络分析探讨新型冠状病毒感染相关脓毒症潜在的关键基因

Identification of key genes participating in the progression of COVID-19-related sepsis based on weighted gene co-expression network analysis

目的 识别2019新型冠状病毒感染(COVID-19)相关脓毒症的关键基因和信号通路。方法 从Gene Expression Omnibus(GEO)数据库下载基因芯片数据。采用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)确定COVID-19和脓毒症的枢纽模块,并将两个模块交叉确定与COVID-19相关脓毒症的共同基因。采用R软件筛选出COVID-19和脓毒症差异表达基因(differentially expressed gene,DEG),同时结合WGCNA和差异分析的结果,得到与COVID-19和脓毒症相关的候选基因,最后将两者取交集得到COVID-19相关脓毒症的关键基因。对与COVID-19相关脓毒症的共同基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,得到基因功能和参与的信号通路。结果 通过WGCNA获得了COVID-19相关枢纽模块和脓毒症相关枢纽模块。将两个模块交叉,共获得49个共同基因。结合WGCNA和差异分析的结果,得出与COVID-19和脓毒症相关的候选基因,通过将候选基因交叉,共筛选出11个关键基因(CCD82、CEACAM8、G6PD、HLA-DMB、HLA-DPA1、IL-1β、LTB4R、LTF、MME、S100A9、TGF-β1)。根据功能富集分析,共同基因主要在免疫和炎症相关通路中增强。结论 本研究通过构建WGCNA方法筛选出COVID-19相关脓毒症的11个关键基因,可能成为潜在的COVID-19相关脓毒症诊疗相关候选靶点。

Objective To identify the key genes and signaling pathways in sepsis associated with the coronavirus disease 2019(COVID-19).Methods The gene chip data were downloaded from the Gene Expression Omnibus(GEO) database.Weighted gene co-expression network analysis(WGCNA) was used to identify the pivot modules of COVID-19 and sepsis,and the two modules were crossed to identify common genes of sepsis associated with COVID-19.By means of R software,differentially expressed genes(DEG) were detected.Combining the results of WGCNA and entially expressed genes,the candidate genes associated with COVID-19 and sepsis were obtained.Finally,the key genes of sepsis associated with COVID-19 were obtained by intersection of the two.Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis were performed on common genes of sepsis associated with COVID-19,and signaling pathways for gene function and involvement were obtained.Results COVID-19 related hub modules and sepsis related hub modules were obtained through WGCNA.By crossing the two modules,a total of 49 common genes were obtained.Combined with the results of WGCNA and difference analysis,candidate genes related to COVID-19 and sepsis were obtained.By crossing candidate genes,a total of 11 key genes were screened out(CCD82,CEACAM8,G6PD,HLA-DMB,HLA-DPA1,IL-1β,LTB4R,LTF,MME,S100A9,TGF-β1).According to functional enrichment analysis,common genes were enhanced mainly in immune and inflammation-related pathways.Conclusions In this study,11 key genes of sepsis related to COVID-19 were screened out by WGCNA method,which may become potential candidate targets related to the diagnosis and treatment of sepsis associated with COVID-19.