先天性心脏传导阻滞药物作用靶点的生物信息学研究  

Bioinformatics Study on Drug Target of Congenital Cardiac Block

作　　者：李自青[1,2] 闫玉清 邢雁霞[1,2] 解瑯明 韩飞宇 张年萍[1,5] LI Zi-qing;YAN Yu-qing;XIN Yan-xia;XIE Lang-ming;HAN Fei-yu;ZHANG Nian-ping(School of Medicine,Shanxi Datong University,Datong Shanxi,037009;Institute of Respiratory and Occupational Disease,Shanxi Datong University,Datong Shanxi,037009;School of Life Science and Biotechnology,Harbin Normal University,Harbin Heilongjiang,150025;Shanxi Weiqida Guangming Pharmaceutical Co.,Ltd,Datong Shanxi,037009;Institute of Cardiovascular Diseases of Integrated Chinese and Western Medicine,Shanxi Datong University,Datong Shanxi,037009)

机构地区：[1]山西大同大学医学院,山西大同037009 [2]山西大同大学呼吸病与职业病研究所,山西大同037009 [3]哈尔滨师范大学生命科学与技术学院,黑龙江哈尔滨150025 [4]山西威奇达光明制药有限公司,山西大同037000 [5]山西大同大学中西医结合心血管病研究所,山西大同037009

出　　处：《山西大同大学学报（自然科学版）》2020年第1期36-40,共5页Journal of Shanxi Datong University(Natural Science Edition)

基　　金：分子发育生物学国家重点实验室2017年开放课题[2018-MDB-KF-07];大同市应用基础研究计划项目[2017134];山西大同大学博士科研启动费资助项目[2016-B-01];山西大同大学校级重点建设学科内科学资助项目[100201];山西省科技厅国际合作项目[201803D421073];山西省科技厅社发项目[201803D31079];大同市重点研发社会发展计划项目[2019080]。

摘　　要：目的通过对CHB药物靶点的研究,为研发CHB特异性治疗药物提供理论依据。方法201609-201812月,构建与先天性心脏传导阻滞直接相关的阳性基因和蛋白集合以及候选阴性集,通过语义相似性计算两个集合间基因的相关性,利用ENDEAVOUR数据库对潜在药物靶点进行功能注释,然后使用GENECODIS对潜在药物靶点蛋白及基因分别进行GO、KEGG、SNP和MicroRNA富集分析。结果挖掘出20个潜在的CHB药物靶点,GO富集分析发现药物靶点蛋白分子功能主要集中于电压门控离子通道活性、转运活性和信号转导活性等;KEGG通路主要富集于钙信号传导通路;SNP富集次数最多的是C/T,出现773次;MicroRNA富集分析发现有15个基因富集于hsa-miR-770-5P上。结论候选阴性集中的20个蛋白可能是CHB潜在的药物靶点,可能为下一步CHB的治疗和药物研发奠定基础。Objective Our research possibly provides a theoretical basis for the development of specific therapeutic drugs for CHB.Methods From September 2016 to December 2018,we constructed positive gene and candidate negative sets of congenital heart block,and used the semantic similarity method based on the GO database performed the functional analysis between the gene sets.ENDEAV⁃OUR database was used to annotate the potential drug target proteins,and then GENECODIS was used to analyze the potential drug tar⁃get proteins and genes by GO,KEGG,SNP and MicroRNA enrichment analysis,respectively.Results We excavated 20 potential drug targets of CHB.GO enrichment analysis showed that the molecular function of drug target protein was mainly concentrated in voltagegated ion channel activity,transport activity and signal transduction activity,and KEGG pathway was mainly enriched in calcium sig⁃nal transduction pathway;The number of SNP enrichment was 773,and 15 genes were found on hsa-miR-770-5P by MicroRNA en⁃richment analysis.Conclusion The 20 proteins in the candidate negative concentration may be potential drug targets for CHB,which may lay a foundation for the treatment and drug development of CHB in the next step.

关 键 词：先天性心脏传导阻滞 药物作用靶点 生物信息学 

分 类 号：R541.76[医药卫生—心血管疾病] R965[医药卫生—内科学]