生物信息学方法分析筛选扩张型心肌病发生发展的关键基因和通路

Identification of key genes and pathways associated with dilated cardiomyopathy development by bioinformatics analysis

目的利用生物信息学方法探究扩张型心肌病潜在的生物标记物和相关富集通路。方法搜索GEO数据库中与扩张型心肌病相关的数据集,提取人心肌细胞的两张芯片GSE42955和GSE1869,然后利用R语言进行差异基因分析、蛋白互作网络分析、鉴定差异表达的核心基因和核心模块并进行基因本体数据库(GO)富集、京都基因与基因组百科全书(KEGG)通路分析。搜索ArrayExpress数据库与扩张型心肌病相关的数据集,提取出人心肌细胞芯片E-TABM-480,验证核心基因和模块在其中的表达情况。结果共验证出10个差异表达基因,即DZIP3、FBXO32、BTBD6、FBXL5、ASB8、COMMD1、LTN1、FBXO21、RCHY1、ARIH2,核心差异基因为DZIP3,经GO和KEGG,上述差异基因的生物学过程主要集中在泛素和蛋白酶体相关的生物学过程和通路中。结论生物信息学分析显示,泛素-蛋白酶系统在扩张型心肌病发病中具有重要作用,其机制尚待进一步研究。

Objective To explore the potential biomarkers and related enrichment pathways of dilated cardiomyopathy(DCM)by bioinformatics methods.Methods The data sets related to DCM in GEO database were searched,and microarray data sets GSE42955 and GSE1869 of human cardiomyocytes were extracted.Then,the differentially expressed genes(DEGS)were analyzed using R language,and the protein-protein interaction network was analyzed to identify the core genes and core modules of differential expression.The gene ontology database(GO)enrichment and Kyoto Gene and Genome Encyclopedia(KEGG)pathway analyses were performed.The data sets related to DCM in ArrayExpress database were searched,and the human cardiomyocytes microarray data set E-TABM-480 was extracted to verify the expressions of core genes and modules.Results We identified 10 DEGS,namely,DZIP3,FBXO32,BTBD6,FBXL5,ASB8,COMMD1,LTN1,FBXO21,RCHY1 and ARIH2,and the core DEG was DZIP3.After GO and KEGG analyses,the GO and KEGG of the above DEGS were mainly related to the ubiquitin-proteasome system.Conclusion Bioinformatics analysis shows that the ubiquitin-proteasome system plays an important role in the pathogenesis of DCM,and the mechanism remains to be further studied.