缺血性心肌病的关键基因鉴定及中药预测

Identification of key genes and prediction of traditional Chinese medicine drugs for ischemic cardiomyopathy

目的:利用生物信息学技术和机器学习算法筛选和分析缺血性心肌病(ICM)的差异表达基因(DEGs),并对干预Hub基因的中药进行预测,为深入探索ICM相关作用机制及干预中药的用药规律提供科学依据。方法:从基因表达综合数据库(GEO)中获取GSE116250数据集中有关ICM和非ICM患者左心室组织切片的数据;利用Limma包筛选2组间的DEGs,对ICM差异表达基因进行基因富集分析(GSEA)。利用加权基因共表达网络分析(WGCNA)获取与临床性状相关最高的基因模块,再与DEGs取交集获得次Hub基因,并对次Hub进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,构建次Hub基因的蛋白质-蛋白质相互作用(PPI)网络并构建随机森林(RF)回归模型及支持向量机-递归特征消除(SVM-RFE)模型,筛选Hub基因,然后应用Coremine Medical数据库来预测干预Hub基因的中药,收集其性味归经、功效等信息。结果:共筛选出805个DEGs和8个Hub基因,基因富集分析结果显示,DEGs在氧化磷酸化、细胞外基质与受体的相互作用、白细胞跨内皮迁移、转化生长因子-β信号通路、Toll样受体信号通路等通路显著富集。中药预测结果显示:药性以平、温、寒为主;药味以苦、甘、辛为主;多归肝、肺、脾经,药物类别以补益药、清热药、利水渗湿药和活血化瘀药为主。结论:本研究筛选出ICM的8个Hub基因,同时还筛选出潜在治疗ICM的靶向中药,其作用机制可能与抗炎、抗心肌凋亡及调节氧化应激反应相关,为ICM的发病机制和遣方用药提供了参考。

Objective:To investigate the differentially expressed genes(DEGs)in ischemic cardiomyopathy(ICM)using bioinformatics techniques and machine learning algorithms,to predict the traditional Chinese medicine(TCM)drugs with an interventional effect on Hub genes,and to provide a scientific basis for further explore the mechanism of action for ICM and the medication rule of TCM drugs.Methods:Gene Expression Omnibus database was used to obtain the data on left ventricular tissue sections in ICM or non-ICM patients in the GSE116250 dataset.Limma package was used to identify the DEGs between the two groups,and Gene Set Enrichment Analysis was performed for these DEGs.The weighted gene co-expression network analysis was used to obtain the gene modules with the highest degree of association with clinical properties,which were intersected with DEGs to obtain secondary Hub genes,and gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for these genes.A protein-protein interaction network was established for secondary Hub genes,and a random forest regression model and a support vector machine-recursive feature elimination model were established.Hub genes were obtained,and Coremine Medical database was used to predict TCM drugs with an interventional effect on Hub genes and collect related information such as nature,taste,meridian entry,a nd function.Results:A total of 805 DEGs and 8 Hub genes were obtained.The Gene Set Enrichment Analysis showed that DEGs were significantly enriched in the pathways of oxidative phosphorylation,interaction between extracellular matrix and receptor,transendothelial migration of leukocytes,transforming growth factor-βsignaling pathway,a nd Toll-like receptor signaling pathway.The prediction of TCM drugs showed that they mainly had a neutral,warm or cold nature and a bitter,sweet or pungent taste,and they mainly entered the liver,lung,and spleen meridians.Tonifying drugs,heat-clearing drugs,diuresis-inducing and dampness-draining drugs,and blood-activating and stasis-resolving drugs were the main types of drugs.Conclusion:This study obtains eight Hub genes for ICM and the targeted TCM drugs for the treatment of ICM,which may have an anti-inflammatory effect,an anti-myocardial apoptosis effect,and an effect in regulating oxidative stress response.The above results provide a reference for the pathogenesis of ICM and prescription and medication for ICM.