冠状病毒感染对造血系统影响及潜在干预药物的生物信息学分析及其对新型冠状病毒肺炎的意义

Bioinformatics Analysis of the Influence of Coronavirus Infection on Hematopoietic System and Potential Intervention Drugs and Their Significance for COVID-19

目的:分析预测冠状病毒感染对造血系统影响及潜在干预药物,探索其对新型冠状病毒肺炎(COVID-19)的意义。方法:利用基因表达数据库(GEO),筛选冠状病毒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表达分析及KEGG和GO富集分析。使用STRING在线分析网站进行PPI网络分析,筛选出核心基因。再应用自主研发的表观精准治疗预测平台(EpiMed)进行疾病、药物和关联靶基因的分析。结果:检索到1个符合标准的数据库,来源于SARS冠状病毒,共筛选出差异基因3 606个,其中表达上调2 148个,下调1 458个。GO富集主要与病毒感染、造血调节、细胞趋化、血小板颗粒内容物分泌、免疫活化和急性炎症反应等有关。KEGG富集主要与造血功能、凝血级联反应、急性炎症和免疫反应等相关。蛋白互作网络分析中,筛选得到PTPRC、ICAM1、TIMP1、CXCR5、IL-1B、MYC、CR2、FSTL1、SOX1、COL3A1共10个核心基因。EpiMed平台筛选出具有潜在干预作用的药物,包括糖皮质激素、肿瘤坏死因子α抑制剂、丹参、西罗莫司、甘草、赤芍、泛昔洛韦、环孢素A、鱼腥草、氟伐他汀等。结论:SARS冠状病毒感染可通过改变一系列基因表达影响造血系统,据此筛选出的潜在干预药物对于COVID-19的基础和临床研究具有一定的参考意义。

Objective:To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs,and explore their significance for coronavirus disease 2019(COVID-19).Methods:The gene expression omnibus(GEO) database was used to screen the whole genome expression data related with coronavirus infection.The R language package was used for differential expression analysis and KEGG/GO enrichment analysis.The core genes were screened by PPI network analysis using STRING online analysis website.Then the self-developed apparent precision therapy prediction platform(EpiMed) was used to analyze diseases,drugs and related target genes.Results:A database in accordance with the criteria was found,which was derived from SARS coronavirus.A total of3606 differential genes were screened,including 2148 expression up-regulated genes and 1458 expression down-regulated genes.GO enrichment mainly related with viral infection,hematopoietic regulation,cell chemotaxis,platelet granule content secretion,immune activation,acute inflammation,etc.KEGG enrichment mainly related with hematopoietic function,coagulation cascade reaction,acute inflammation,immune reaction,etc.Ten core genes such as PTPRC,ICAM1,TIMP1,CXCR5,IL-1 B,MYC,CR2,FSTL1,SOX1 and COL3 A1 were screened by protein interaction network analysis.Ten drugs with potential intervention effects,including glucocorticoid,TNF-α inhibitor,salvia miltiorrhiza,sirolimus,licorice,red peony,famciclovir,cyclosporine A,houttuynia cordata,fluvastatin,etc.were screened by EpiMed plotform.Conclusion:SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes.The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.