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

作　　者：张钧栋 杨波[2] 陈浩然 迟小华 陈熙勐 智鹏 张皓旻 王紫宁 郭斌 王毅兴[5] 孙万军 卢学春 ZHANG Jun-Dong;YANG Bo;CHEN Hao-Ran;CHI Xiao-Hua;CHEN Xi-Meng;ZHI Peng;ZHANG Hao-Min;WANG Zi-Ning;GUO Bin;Wang Yi-Xing;SUN Wan-Jun;LU Xue-Chun(Medical School of Chinese PLA,Beijing 100S53,China;Department of Hematology,The Second Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Department of Pharmacy,Rocket Force General Hospital,Beijing 10008&China;Department of Personnel,Shanxi Cardiovascular Hospital,Taiyuan 030024,Shanxi Province,China;Department of Traditional Chinese Medicine,Shanghai East Hospital,Tongji University,Shanghai 200120,China;Department of Hematology,Rocket Force General Hospital,Beijing 100088,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第二医学中心血液病科,国家老年疾病临床医学研究中心,北京100853 [3]火箭军特色医学中心药剂科,北京100088 [4]山西省心血管病医院人事科,山西太原030024 [5]同济大学附属东方医院中医科,上海200120 [6]火箭军特色医学中心血液科,北京100088

出　　处：《中国实验血液学杂志》2021年第3期975-982,共8页Journal of Experimental Hematology

基　　金：2017年度国家老年疾病临床医学研究中心招标课题(NCRCG-PLAGH-2017011);解放军总医院转化医学项目(2017TM-020);军队重点保健专项(18BJZ32);2019年度保健专项科研课题(19BJZ28)。

摘　　要：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.

关 键 词：SARS冠状病毒 新型冠状病毒肺炎 造血系统 药物 生物信息学 

分 类 号：R563.1[医药卫生—呼吸系统]