扩张型心肌病相关基因的生物信息学研究

The Study of Bioinformatics of Dilated Cardiomyopathy Related Genes

目的筛查扩张型心肌病相关的关键基因,为扩张型心肌病的发病机制、诊断以及治疗靶点筛选提供参考。方法从美国国家生物信息中心(NCBI)公共数据平台基因表达数据库(GEO)获得数据集GSE42955,使用GEO2R在线分析工具筛选出心肌病相关差异性表达基因,利用DAVID6.7生物信息学资源数据库进行基因(GO)和KEGG通路富集分析,STRING数据库和Cytoscape 3.8.0软件进行蛋白-蛋白相互作用(PPI)网络分析,利用插件MCODE和CytoHubba获得连接度最高的前10位的基因作为关键基因。结果筛选出差异基因57个,其中下调25个,上调32个,主要分布于细胞膜和细胞外隙,通过对细胞因子的反应、脂质的反应、有机物的反应、脂多糖应答、节律过程、对细菌来源分子的反应、细胞表面受体信号通路、细胞因子介导的信号通路等生物功能,诱导扩张型心肌病的发生;涉及的分子功能有双加氧酶活性、受体结合、核启动子结合。KEGG富集显示,与心肌病相关的转录基因主要在非洲锥虫病、疟疾、TNF信号通路等。结论最后筛选出10个关键的核心基因,其中ICAM-1、VCAM-1和GBP-1与扩张型心肌病相关,其他基因的功能还需进一步在动物实验和临床中验证。

Objective Screening for hub genes of dilated cardiomyopathy,providing a theoretical basis for pathogenesis,diagnosis and therapeutic targets of dilated cardiomyopathy.Methods The gene chip dataset GSE42955 were downloaded from the NCBI public data platform GEO.GEO2R online analysis tool was used to identify DCM related differential expressed genes;DAVID 6.7 bioinformatics resource database was used to carry out GO and KEGG enrichment pathways,STRING database and Cytoscape 3.8.0 software were used to analyses the protein-protein interaction(PPI)networks,finally,the plug-in MCODE and CytoHubba were used to obtain the hub genes.Results A total of 57 differential expressed genes were identified from DCM,consisting of 25 downregulated genesand 32 up-regulated genes,which mainly distributed in membrane and extracellular matrix,caused DCM via biological processes such asrhythm process,cytokine reaction,lipid,organic matter and lipopolysaccharide responses,source of bacteria molecular reaction,cell surface receptors signaling pathways involved in dioxygenase activity,receptor binding and nuclear promoter binding.KEGG analysis showed that thedifferential expression geneswas enriched in African trypanosomiasis,malaria,and TNF signaling pathways.Conclusion The research results showed 10 key genes were screenedout,ICAM-1(intercellular adhesion molecule-1),VCAM-1(vascular cell adhesion molecule-1)and GBP-1(interferon-induced guanylate binding protein 1)were associated with dilated cardiomyopathy.The functions of other genes need to be further verified in animal experiments and clinical trials.