摘要
目的鉴别新型冠状病毒肺炎(COVID-19)患者外周血差异表达先天免疫基因并探讨其与24种免疫细胞丰度的关系。方法从GEO数据库下载GSE161731表达谱数据集,采用GENCODE人类基因组GRCh38注释文件进行基因重注释,以校正后的P<0.05及|log 2 FC|>2为阈值筛选COVID-19患者与健康对照人群间的差异表达基因(DEGs)。采用InnateDB数据库中的人类先天免疫基因集鉴定差异表达先天免疫基因(DEIIGs)并采用Metascape平台进行GO和KEGG功能富集分析,使用ImmuCellAI平台预测24种免疫细胞丰度。结果共筛选出88个DEGs,其中上调基因49个,下调基因39个,UCHL1、IFI27、PPARG、CCL2、IGF1、BIRC5、IGHG1是鉴别出的7个DEIIGs。GO分析富集于STAT受体信号通路、淋巴细胞活化的正向调控和细胞因子介导的信号通路;KEGG分析富集于癌症代谢途径。COVID-19患者外周血幼稚CD4^(+)T细胞、辅助性T细胞1(Th1)和中枢记忆性T细胞(Tcm)丰度降低,而Ⅰ型调节性T细胞(Tr1)和天然调节性T细胞(nTreg)丰度高于健康对照人群(P<0.05)。幼稚CD4^(+)T细胞丰度与PPARG、IGHG1表达呈负相关,Tr1丰度与IGHG1表达呈正相关,nTreg丰度与BIRC5表达呈正相关,Th1与IFI27表达呈正相关。结论幼稚CD4^(+)T细胞、Tr1、nTreg和Th1丰度可能分别与PPARG、IGHG1、BIRC5和IFI27基因表达改变有关。
Objective Identifying differently expressed innate genes in peripheral blood of coronavirus disease 2019(COVID-19)patients and exploring their associations with 24-type immune cells.Methods GSE161731 dataset performed by RNAseq from GEO database was downloaded and reannotated by human genome annotation file GRCh38 in GENCODE.Differentially expressed genes(DEGs)between COVID-19 patients and healthy controls were screened by the threshold of corrected P<0.05 and|log_(2) FC|>2.Differentially expressed innate immunity genes(DEIIGs)were identified by the InnateDB and GO and KEGG functional enrichment analysis was performed by the Metascape platform.ImmuCellAI was utilized to predict the abundances of 24-type immune cells.Results A total of 88 DEGs including 49 upregulated and 39 downregulated genes were identified,and UCHL1,IFI27,PPARG,CCL2,IGF1,BIRC5,IGHG1 were the confirmed seven DEIIGs.GO analysis enriched in receptor signaling pathway via STAT,positive regulation of lymphocyte activation,and cytokine-mediated signaling pathway,while pathways in cancer were the enriched KEGG metabolism pathways.Compared to healthy controls,the abundances of naive CD4^(+)T cell,T helper 1 cell(Th1),central memory T cell(Tcm)were decreased in the peripheral blood of COVID-19 patients,whereas type 1 regulatory T cell(Tr1)and natural regulatory T cell(nTreg)were enhanced(P<0.05).The abundance of na ve CD4^(+)T cell was negatively associated with the expression of PPARG and IGHG1,the abundance of Tr1 was positively associated with the expression of IGHG1,the abundance of nTreg was positively associated with the expression of BIRC5,and Th1 was positively associated with IFI27.Conclusion The abundances of naive CD4^(+)T cell,Tr1、nTreg,and Th1 plausibly associated with the expression of PPARG,IGHG1,BIRC5 and IFI27,respectively.
作者
余耀华
张兵
张华
YU Yaohua;ZHANG Bing;ZHANG Hua(Ward 1 of Pulmonary and Critical Care Medicine,ZhengZhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450000,China;Department of Urology,ZhengZhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450000,China)
出处
《河南医学研究》
CAS
2022年第21期3841-3845,共5页
Henan Medical Research
基金
河南省医学科技攻关计划联合共建项目(LHGJ2018020776)。
