人肺上皮细胞抗新型冠状病毒感染的基因组学研究

Genomics study of human lung epithelial cells against new coronavirus SARS-CoV-2 infection

目的基于全基因组高通量测序数据,采用基因组学和生物信息学方法分析新型冠状病毒肺炎(COVID-19)患者肺组织上皮细胞的基因表达变化,探讨新型冠状病毒(SARS-CoV-2)对人体肺组织上皮细胞的影响及可能机制,为SARS-CoV-2对肺组织致病机制的探索提供一定理论依据。方法检索获得公共数据集GSE160435,采用Network analyst、Cytoscape 3.7.2、String 11.0等软件对数据进行分析,筛选COVID-19患者肺组织上皮细胞差异表达基因,进行基因功能(gene ontology,GO)和信号通路KEGG(kyoto encyclopedia of genes and genomes)富集分析,建立蛋白互作网络(protein-protein interactions network,PPI)、肺组织特异性差异表达基因(DEGs)的PPI交互作用网络、DEG-microRNA调控网络、转录因子(transcription factor,TF)-DEG调控网络、环境化学物-DEG调控网络。结果COVID-19患者肺组织上皮细胞的基因表达明显改变,共发现324个DEGs,其中上调112个(34.57%),下调212个(65.43%);富集分析显示,DEGs主要参与对病毒相关的防御反应等生物学过程,主要涉及蛋白质消化与吸收、抗人乳头瘤病毒感染等信号通路;DEGs和肺组织特异性的PPI网络显示,PDGFRB和KIT为核心蛋白;hsa-miR-340与DEGs存在靶向交互关系;表明HOXB4、ISG15等相关基因受TF调节;DEGs与环境化学物镍、雌二醇等有交互作用。结论COVID-19患者肺组织上皮细胞的基因表达显著改变,PDGFRB、KIT、MMP9等蛋白或基因可能在肺组织的防御免疫机制中发挥着重要作用;Micro-RNA、TF、信号通路分子、环境化学物、肺组织特异性基因在上述过程中也起到一定作用。这为探索SARS-CoV-2对肺组织致病机制的研究及制定临床预防、诊断和治疗措施提供了新思路。

Objective Based on the high-throughput sequencing data of the whole genome,genomics and bioinformatics analyses were made to analyze the gene expression changes in the epithelial cells of the lung tissue from patients with coronavirus disease 2019(COVID-19),and explore the effects of the new coronavirus SARS-CoV-2 on human lungs.This study can provide a theoretical basis for the exploration of SARS-CoV-2 on the pathogenesis of lung tissue.Methods The public data set GSE160435 was retrieved.The data were analyzed by Network analyst,Cytoscape 3.7.2,String 11.0,and other software.The differentially expressed genes were screened,gene function(Gene Ontology,GO)and signal pathway KEGG(Kyoto Encyclopedia of Genes and Genomes)enrichment analysis were carried out.We established the Protein-protein Interactions Network(PPI),PPI of lung tissue-specific DEGs,DEG microRNA regulatory network,Transcription Factor(TF)-DEG regulatory network,and environmental chemicals DEGs regulatory network.Results We found 324 DEGs in the lung epithelial cells of patients with COVID-19,of which 112(34.57%)were upregulated and 212(65.43%)were downregulated.Enrichment analysis showed that DEGs were mainly involved in biological processes such as virus-related defense response,mainly involved in protein digestion and absorption,anti-human papillomavirus infection and other signaling pathways.Specific PPI network closely related to DEGs and lung tissue showed that PDGFRB and KIT were core proteins;hsa-mir-340 had targeted interaction with DEGs.It indicated that HOXB4,ISG15 and other related genes were regulated by transcription factors;DEGs interacted with environmental chemicals such as nickel and estradiol.Conclusion The gene expression pattern of lung epithelial cells in lung tissue of COVID-19 patients has changed significantly.Proteins or genes such as PDGFRB,MMP9 and KIT may play a vital role in the defense immunity of lung tissue.Micro-RNA,TF,signaling pathway molecules,environmental chemicals,and lung tissue-specific genes also play a role in the above-mentioned process.This study provides new ideas for exploring the pathogenic mechanism of SARS-CoV-2 on lung tissue and formulating clinical prevention,diagnosis and treatment measures.