重症COVID-19肺炎肺纤维化关键基因的筛选

Identification of key genes for pulmonary fibrosis in severe COVID-19 patients

目的 通过生物信息学方法筛选重症COVID-19肺炎患者肺纤维化的关键基因,并预测重症COVID-19肺炎肺纤维化的潜在治疗性中药。方法 从GEO数据库中下载重症COVID-19肺炎肺纤维化的表达矩阵(GSE206788),通过R语言确定重症COVID-19肺炎肺纤维化组与正常对照组的差异表达基因(DEGs),进行基因本体(gene ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,同时进行蛋白质互作网络分析,5种算法取交集得到关键基因,通过Coremine Medical平台筛选可能的治疗中药。结果 共筛选出249个差异基因,GO功能注释结果显示,DEGs主要在信号转导、免疫应答、炎症反应、质膜、细胞外区域、蛋白质结合功能等富集。KEGG通路分析结果显示,DEGs主要在癌症、磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等信号通路富集。共筛选出10个关键基因:IL-10、IRF4、JUN、PTK2、TNF、KDR、CXCL8、SMAD3、NOTCH1、RPS27A,通过Coremine Medical平台筛选得到黄芩、黄芪、茶树根、人参、灵芝、丹参等多味具有潜在疗效的中药。结论 本研究筛选出了重症COVID-19肺炎肺纤维化的关键基因及预测了潜在的治疗性中药,为临床治疗的研究提供了参考。

Objective Identification of key genes for pulmonary fibrosis in severe COVID-19 patients by bioinformatics and prediction potential traditional Chinese medicine drugs.Methods The expression matrix of severe COVID-19 pneumonia pulmonary fibrosis(GSE206788)was downloaded from the GEO database,and the different-expressed genes(DEGs)between the severe COVID-19 pneumonia pulmonary fibrosis group and normal control group were determined by R language.The gene ontology(GO)function annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was conducted,the protein interaction network analysis was also conducted,and the key genes were obtained by the intersection of the five algorithms.The possible therapeutic TCM was screened through the Coremine Medical platform.Results A total of 249 differential genes were screened,and the GO functional annotation results showed that DEGs were mainly enriched in signal transduction,immune response,inflammatory response,plasma membrane,extracellular region,and protein binding function.KEGG pathway analysis showed that DEGs were mainly involved in cancer,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),mitogen-activated protein kinase(MAPK),and other signaling pathways are enriched.A total of 10 key genes were screened out:IL-10,IRF4,JUN,PTK2,TNF,KDR,CXCL8,SMAD3,NOTCH1,and RPS27A.Multi-flavor Chinese medicines with potential curative effects such as Baicalensis,Astragalus,tea tree root,ginseng,Ganoderma lucidum,and salvia miltiorrhiza were selected through the Coremine Medical platform.Conclusion This study screened the key genes and predicted the potential therapeutic traditional Chinese medicine for pulmonary fibrosis caused by severe COVID-19 pneumonia,providing a reference for clinical treatment research.