哮喘相关基因与治疗药物的生物信息学分析

Bioinformatic Analysis of Related Genes and Therapeutic Drugs of Asthma

目的:通过生物信息学技术比较哮喘患者与健康人的基因芯片数据,初步鉴定与哮喘相关的基因以及治疗哮喘的潜在药物。方法:从基因表达数据库下载GSE74986基因芯片,使用GEO2R分析得出差异表达基因,采用Morpheus制作差异表达基因的热图;通过DAVID 6.8对差异表达基因进行基因本体及京都基因与基因组百科全书分析,使用String 10.5构建蛋白质-蛋白质相互作用网络,筛选核心基因。进一步使用Cytoscape 3.6.1的插件MCODE对差异表达基因进行模块分析。通过医学本体信息检索平台筛选治疗哮喘的小分子药物。结果:筛选出510个差异表达基因,包括29个上调基因和481个下调基因。差异表达基因生物过程与通路主要富集在染色质沉默、核糖核酸聚合酶Ⅱ启动子的转录调节、蛋白质转运、信使核糖核酸加工、核糖核酸剪接以及泛素介导的蛋白水解、内质网中的蛋白质加工、核糖核酸转运、髓样分化因子依赖性Toll样受体信号通路、血小板激活、核苷酸结合寡聚化结构域样受体信号通路等。共得出9个核心基因,包括T-复合蛋白1θ亚基(CCT8),T复合物蛋白1α亚单位(TCP1),26S蛋白酶调节亚单位S10B(PSMC6),热休克蛋白90α(HSP90A) A1,细胞周期蛋白C(CCNC),HSP90AB1,26S蛋白酶体非ATP酶调节亚基6(PSMD6),泛素特异性蛋白酶14(USP14),真核细胞翻译起始因子4E(EIF4E)。得出2个重要模块,模块里的基因主要涉及剪接体和泛素介导的蛋白水解、蛋白修饰以及核糖核酸修饰等生物过程。治疗哮喘的潜在小分子药物有茴香霉素和金雀异黄素等。结论:差异表达基因和核心基因促进了对哮喘发病分子机制的理解,为哮喘的诊治提供了潜在的基因靶标与治疗药物。

Objective: Bioinformatic analysis was used to compare the gene expression profile between asthma patients and healthy people,and the gene characteristics of asthma were preliminarily identified and the potential mechanism and drugs were revealed.Method: The GSE74986 gene expression profile was downloaded from the gene expression omnibus(GEO) and the differentially expressed genes(DEGs) were analyzed by GEO2R.Then the gene heat map of DEGs was made by Morpheus,and their gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) analysis were performed by DAVID 6.8.Moreover,the proteinprotein interaction(PPI) network and hub genes were constructed by String 10.5.Finally,the significant modules were analyzed by MCODE in Cytoscape 3.6.1,small molecule drugs related to asthma were screened through Coremine Medical.Result: A total of 510 DEGs were screened,including 29 up-regulated genes and 481 downregulated genes.DEGs were mainly involved in these biological processes and pathways,including chromatin silencing,transcriptional regulation of RNA polymerase Ⅱ promoter,protein transport,messenger RNA(mRNA)processing,RNA splicing,ubiquitin-mediated proteolysis,protein processing in the endoplasmic reticulum,RNA transport,and myeloid differentiation factor(MyD)-dependent Toll-like receptor signaling pathway,platelet activation,nucleotide binding oligomerization domain(NOD)-like receptor signaling pathway and so on.A total of 9 hub genes were obtained,including T-complex protein 1 subunit theta(CCT8),T-complex protein 1 subunit alpha(TCP1),26 S protease regulatory subunit S10 B(PSMC6),heat shock protein 90 alpha(HSP90 A) A1,cell cycle protein C(CCNC), HSP90 AB1,26 S proteasome non-ATPase regulatory subunit 6(PSMD6),ubiquitin-specific protease 14(USP14) and eukaryotic translation initiation factor 4 E(EIF4 E).Two important modules were obtained.The genes in two modules mainly involved these biological process,such as splice,ubiquitin-mediated proteolysis,protein modification,RNA modification and so on.Some potential molecular drugs for the treatment of asthma,such as anisomycin and genistein,have been developed.Conclusion: DEGs and hub genes can contribute to understanding the molecular mechanism of asthma and providing potential therapeutic targets and drugs for the diagnosis and treatment of asthma.