| 郑阳,王全意.利巴韦林和干扰素-α联合应用治疗中东呼吸综合征冠状病毒感染的生物信息学分析[J].Chinese journal of Epidemiology,2016,37(2):291-293 |
| 利巴韦林和干扰素-α联合应用治疗中东呼吸综合征冠状病毒感染的生物信息学分析 |
| Bioinformatics analysis on molecular mechanism of ribavirin and interferon-α in treating MERS-CoV |
| Received:July 31, 2015 |
| DOI：10.3760/cma.j.issn.0254-6450.2016.02.028 |
| KeyWord: 中东呼吸综合征 利巴韦林 干扰素-α 信号通路 |
| English Key Word: Middle East Respiratory Syndrome Ribavirin Interferon-α Signaling pathway |
| FundProject:北京市科技计划(D141100003114002) |
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| Abstract: |
| 目的 通过生物信息学分析探讨联合应用利巴韦林和干扰素-α防治中东呼吸综合征冠状病毒(MERS-CoV)感染的分子机制。方法 在Array Express数据库中查找MERS-CoV相关的基因芯片数据,利用Agilent GeneSpring GX软件对芯片数据进行处理分析。在比较毒理基因组学数据库(CTD)中查找利巴韦林和干扰素-α作用于人体的靶基因位点,利用PANTHER TOOL和DAVID平台分别对基因芯片数据和药物靶基因进行GO功能注释和信号通路分析。结果 检索数据库得到MERS-CoV感染相关的mRNA表达谱芯片数据,以及27个利巴韦林和干扰素-α作用的靶基因。对MERS-CoV感染相关mRNA表达谱数据进行聚类分析可分为两组基因群,即基因表达随病毒感染时间逐渐上升或下降。GO分析显示,药物靶基因与基因芯片数据共同涉及10个生物学过程,主要包括细胞生理、代谢、免疫、生物调节、应激反应等。药物靶基因、基因芯片第一组基因群(随病毒感染时间表达上升)和第二组基因群(随病毒感染时间表达下降)参与的信号通路分别为9、3和23个,其中仅前二者有共同参与的信号通路共7个,主要与识别病原体、促进细胞因子释放、生成自身免疫应答等有关。结论 利巴韦林和干扰素-α联合应用可通过干预多个信号通路中的位点起到治疗MERS-CoV感染的作用,MERS-CoV感染相关基因芯片数据中随感染时间表达水平下降的基因可作为药物靶基因为筛选治疗MERS感染的新型药物提供参考信息。 |
| English Abstract: |
| Objective To study the molecular mechanism of ribavirin and interferon-α in the treatment of Middle East Respiratory Syndrome(MERS) by bio-informatic Methods.Methods MERS-CoV-related microarray data was searched from Array Express database and analyzed by Agilent GeneSpring GX software.Target genes of ribavirin and interferon-α were acquired from Comparative Toxicogenomics Database(CTD).PANTHER TOOL and DAVID platform were used for the analysis of GO and Pathway.Results One set of MERS-CoV related microarray data and 27 target genes of ribavirin and interferon-α were acquired from the online databases.Data on Genes from microarray were divided into two time-related gene clusters by using the Unsupervised Hierarchical Clustering.Data from the GO analysis indicated that the target genes of ribavirin and interferon-α as well as the genes from the microarray were mainly enriched in 10 biological processes, including cellular process, metabolic process, immune system process and biological regulation, et al.Data on drug target genes, first and second cluster of microarray would involve 9, 3 and 23 signaling pathways respectively, and only the former two showed 7 common pathways, which were related to pathogen recognition, cytokine release and autoimmune response.Conclusion Ribavirin in combination with interferon-α might have therapeutic effects on MERS patients through several signaling pathways.Genes in the second cluster might serve as target genes to be used for screening of new drugs in treating the MERS-CoV infection. |
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