摘要
目的通过分析α干扰素抗病毒相关全基因组表达谱,探索其对新型冠状病毒肺炎的潜在治疗意义。方法应用R语言对来自基因表达数据库(gene expression omnibus,GEO)的α干扰素相关的全基因组表达谱开展差异分析、富集分析、蛋白互作分析,再应用自主研发的表观精准治疗预测平台(epigenomic precision medicine prediction platform,EpiMed),寻找与α干扰素调控基因表达谱呈负相关的疾病类型,以及呈正相关的药物。结果α干扰素对基因组表达谱影响复杂,其调控的核心基因有OAS1、MX1、OASL、ISG15、IST1、IRF7等,参与病毒生命周期的负调控、B细胞受体信号通路、肝炎、双链RNA绑定、人类免疫缺陷病毒感染,以及JAK-STAT信号通路等。进一步分析,α干扰素调控的基因组表达谱与社区获得性肺炎和脓毒症等感染性疾病呈高度负相关,而与利托那韦、利巴韦林、奈韦拉平、氟伐他汀呈高度正相关。结论基于α干扰素抗病毒相关基因组表达谱的分析对于探索新型冠状病毒肺炎潜在治疗药物具有一定的借鉴意义。
Objective Explore the potential therapeutic significance ofα-interferon antiviral-related genome-wide expression profiles for coronavirus disease 2019.Methods Application of R language to differential analysis,enrichment analysis,and protein interaction analysis of interferon-alpha-related whole-genome expression profiles from the gene expression omnlbus(GEO).Applied epigenomic precision medicine prediction platform(EpiMed),to explore disease types that are negatively related to alpha interferon-regulated gene expression profiles,and drugs that are positively related.Results The effects of interferon-alpha on the transcriptome are complex.The effects of core genes OAS1,MX1,OASL,ISG15,IST1,IRF7,etc.include negative regulation of the viral life cycle,B cell receptor signaling pathway,hepatitis,double-stranded RNA binding,human immunodeficiency virus infection.And related pathways such as the JAK-STAT signaling pathway.At the same time,the transcriptome tag of interferon-alpha is highly negatively related to infectious diseases such ascommunity-acquired pneumonia and sepsis,and highly positively related to the guidelines published by the drug Ritonavir、Ribavirin、Nevirapine and Fluvastatin.Conclusion The analysis of the expression profile of the anti-virus related genomes ofα-interferon has certain reference significance for exploring new potential therapeutic drugs for coronavirus pneumonia(NCP).
作者
智鹏
杨波
陈浩然
陈熙勐
迟小华
张钧栋
郭斌
李卓阳
刘格良
张皓旻
王毅兴
卢学春
ZHI Peng;YANG Bo;CHEN Haoran;CHEN Ximen;CHI Xiaohua;ZHANG Jundong;GUO Bin;LI Zhuoyang;LIU Geliang;ZHANG Haomin;Wang Yixing;LU Xuechun(Department of Hematology,the Second Medical Center Chinese PLA General Hospital,National Center for Clinical Research of Geriatric Diseases,Beijing 100853,China;Pharmacy department,Chinese PLA characteristic medical center,Beijing 100088,China;Management School of Shanxi Medical University,Taiyuan Shanxi 030002,China;Personnel department of shanxi cardiovascular hospital,Taiyuan Shanxi 030024,China;Department of traditional Chinese medicine,dongfang hospital affiliated to tongji university,Shanghai 200120,China)
出处
《转化医学杂志》
2020年第6期368-372,共5页
Translational Medicine Journal
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)
中国人民解放军总医院转化医学项目(2017TM-020)
上海浦东新区卫健委学科带头人计划(PWRd2019-04)
上海浦东新区中医治未病高峰学科(PDZY-2018-0603)
2019年度保健专项科研课题(19BJZ28)
军队保健人群老年共病的新型危险因素预警及干预研究(18BJZ32)。