新型冠状病毒感染致造血损伤及潜在治疗药物的生物信息学分析

Bioinformatics analysis of hematopoietic injury and potential therapeutic drugs associated withSARS-CoV-2 infection

目的分析预测新型冠状病毒(SARS-CoV-2)感染所致造血损伤及潜在的治疗药物,为临床救治SARSCoV-2感染所致造血损伤提供理论依据。方法利用基因表达数据库(GEO)筛选SARS-CoV-2感染相关的全基因组表达数据,使用R语言包对数据进行差异分析以及基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过蛋白-蛋白相互作用数据库(STRING)在线分析网站进行蛋白互作(PPI)网络分析,筛选核心基因。应用自主研发的表观精准治疗预测平台(EpiMed)进行疾病、药物和关联靶基因分析。结果共筛选出差异基因222个,其中上调172个,下调50个。GO富集分析结果显示,差异基因主要与Ⅰ型干扰素反应、细胞周期调节、炎性细胞迁移、先天免疫反应、血液微粒和囊泡分泌、趋化因子及其受体等有关。KEGG富集分析结果显示,差异基因主要与病毒感染、心肌损伤、补体及凝血级联、细胞趋化、血小板活化、急性炎症、免疫反应、细胞信号转导等相关信号通路有关。PPI网络分析筛选得到STAT1、IL-6、IRF7、TNF、MX1、ISG15、IFIH1、IRF9、DDX58和GBP1等10个核心基因。EpiMed平台筛选出具有潜在治疗作用的药物包括冬凌草、西罗莫司、糖皮质激素、鱼腥草、何首乌、赤芍、维甲酸、甘草、环孢素A、氟伐他汀等。结论SARS-CoV-2感染可通过改变一系列基因的表达从而影响造血系统,据此筛选出的潜在治疗药物可为新型冠状病毒肺炎(COVID-19)的基础和临床研究提供参考。

Objective To analyze and predict hematopoietic injury caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and potential therapeutic drugs,and to provide theoretical basis for clinical treatment of the hematopoietic injury.Methods The gene expression omnibus(GEO)database was used to screen the whole genome expression data related to SARS-CoV-2 infection.The R language package was used for differential expression analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis.The core genes were screened by protein-protein interaction (PPI) network analysis using STRING online analysis website. Then the self-developed apparentprecision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes. Results A total of 222differential genes were screened, including 172 up-regulated and 50 down-regulated. GO enrichment analysis suggested that gene ismainly related to type I interferon response, cell cycle regulation, inflammatory cell migration, innate immune response, secretion ofblood particles and vesicles, chemokines and their receptors. KEGG enrichment analysis suggested that gene is mainly related to viralinfection, myocardial injury, complement and coagulation cascade, cell chemotaxis, platelet activation, acute inflammation, immuneresponse, cellular signal transduction and so on. Ten core genes such as STAT1, IL-6, IRF7, TNF, MX1, ISG15, IFIH1, IRF9, DDX58and GBP1were screened by PPI network analysis. EpiMed screened 10 drugs with potential intervention effects, including Rabdosiarubescens, sirolimus, glucocorticoid, Houttuynia cordata, Polygonum multiflorum, Red peony, tretinoin, Glycyrrhiza, cyclosporineA, fluvastatin and so on. Conclusions SARS-CoV-2 infection can damage the hematopoietic system by changing the expressionof a series of genes. The potential intervention drugs screened from this have certain reference significance for the basic and clinicalresearch of coronavirus disease 2019 (COVID-19).