基于生物信息学方法的SARS-CoV-2和MERS-CoV差异表达基因分析

Bioinformatics analysis of differentially expressed genes in SARS-CoV-2 and MERS-CoV

目的旨在筛选严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染人体后的关键基因,探究其发病机制,为新型冠状病毒肺炎(COVID-19)的诊疗提供理论依据。方法对SARS-CoV-2和中东呼吸综合征冠状病毒(MERS-CoV)感染人体后的基因表达进行差异分析,通过京都基因与基因组百科全书(KEGG)和基因本体论(GO)富集分析差异基因或蛋白的功能注释和信号通路。在Cytoscape中构建SARS-CoV-2差异基因的蛋白相互作用网络,通过权重值(weight)比较选取前30作为关键基因。结果发现肿瘤坏死因子(TNF)信号通路在MERS-CoV感染的多个时间点及SARS-CoV-2中均有显著富集,并发现TNF信号通路的相关基因肿瘤坏死因子α诱导蛋白3(TNFAIP3)在差异基因中连接性较强。结论对MERS-CoV和SARS-CoV-2差异基因表达进行分析,找出SARSCoV-2的关键基因TNFAIP3,推测通过调节其表达水平从而抑制炎症反应,为缓解或治疗COVID-19提供新的思路。

Objective To screen the key genes after infection of severe acute respiratory syndrome coronavirus 2(SARSCoV-2),explore its pathogenesis,and provide data for the diagnosis and treatment of new coronavirus pneumonia(COVID-19).Methods A differential analysis of the gene expression of SARS-CoV-2 and Middle East respiratory syndrome coronavirus(MERS-CoV)was conducted.The Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene ontology(GO)were used to analyze the functional annotations and signal pathways of differential genes or proteins.The protein interaction network of SARS-CoV-2 differential genes was constructed in Cytoscape.The top 30 were selected as key genes via weight comparison.Results It was found that the tumor necrosis factor(TNF)signaling pathway was significantly enriched at multiple time points of MERS-CoV infection and SARS-CoV-2.At the same time,the downstream gene of TNF signaling pathway,tumor necrosis factor alpha inducing protein 3(TNFAIP3),had strong connectivity.Conclusion The differential gene expressions of MERS-CoV and SARS-CoV-2 are analyzed using bioinformatics methods,and the key gene TNFAIP3 of SARS-CoV-2 is found.It is speculated that SARS-CoV-2 can be treated by regulating the expression level of TNFAIP3,which offers a new idea for the treatment of SARS-CoV-2.