摘要
目的筛查肥厚型心肌病相关的关键基因,为肥厚型心肌病的发病机制提供理论依据。方法从高通量基因表达(GEO)数据库中检索包含106例肥厚型心肌病样本及39例对照组样本的高通量测序数据集GSE36961。利用R软件筛选肥厚型心肌病组织和正常组织间差异表达的基因,通过WGCNA构建差异基因的加权重共表达网络,筛选出与肥厚型心肌病相关的模块,对模块中的基因行功能富集分析,并应用STRING数据库构建蛋白互作网络筛选出关键基因。结果从数据集中筛选出8002个差异表达基因(P<0.05),通过WGCNA构建出差异基因的加权重共表达网络,筛选出两个与肥厚型心肌病相关的模块:青色模块(Pearson cor=0.77,P=4e-29)和紫红色模块(Pearson cor=0.76,P=2e-28)。前者基因功能主要富集在能量代谢,后者基因功能主要富集在血管形成。通过蛋白质相互作用网络分析获得32个基因及157个互作关系,从中筛选出与肥厚型心肌病相关的关键基因,提示肥厚型心肌病可能与炎症反应相关。结论本研究通过系统性分析肥厚型心肌病患者的高通量测序数据集,筛选出可能与肥厚型心肌病有关的目标基因32个,再筛选出关键基因10个,其中甲酰肽受体2(formyl peptide receptor 2,FPR2)、毒蕈碱型胆碱受体M2(cholinergic receptor musca⁃rinic 2,CHRM2)与心肌炎症反应相关,余基因的作用仍需在未来的细胞及动物实验中得到进一步的验证。
Objectives To screen out the hub genes of hypertrophic cardiomyopathy,in order to provide a theoretical basis for the study of the pathogenesis of hypertrophic cardiomyopathy.Methods The expression profile data GSE36961,which included 106 cases of hypertrophic cardiomyopathy and 39 cases of control group,was searched in GEO database.The differentially-expressed genes(DEGs)between hypertrophic cardiomyopathy and normal tissues were analyzed by R software,and the weighted co-expression network of DEGs was constructed by WGCNA to identify the modules related to hypertrophic cardiomyopathy.Functional enrichment analysis was used in the genes of the module,and the STRING database was used to construct the protein interaction network,so as to screen out the hub genes.Results A total of 8002 DEGs were screened from the expression profile data(P<0.05).The weighted co-expression network of DEGs was constructed by WGCNA,and two modules related to hypertrophic cardiomyopathy were screened,which were cyan module(Pearson cor=0.77,P=4e-29)and the magenta module(Pearson cor=0.76,P=2e-28).The gene function in the cyan module was mainly enriched in energy metabolism,and the gene function in the magenta module was mainly enriched in angiogenesis.Thirty two genes and 157 interactions were obtained by protein-protein interaction network analysis,and then we screened out the hub genes.The result of the hub genes suggested that hypertrophic cardiomyopathy may be related to inflammation.Conclusions In this study,by systematically analyzing the high-throughput sequencing data sets of patients with hypertrophic cardiomyopathy,32 target genes were screened out,and 10 key genes were screened,of which formyl peptide receptor 2(FPR2),cholinergic receptor muscarinic 2(CHRM2)were associated with myocardial inflammation.The role of the remaining genes needs to be further verified in future cell and animal experiments.
作者
黄蕾
秦显雨
吴岳恒
林吉进
HUANG Lei;QIN Xian-yu;WU Yue-heng;LIN Ji-jin(The Second School of Clinical Medicine,Southern Medical University,Guangzhou 510515,China;Department of Cardiology,Guangdong Cardiovascular Institute,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China)
出处
《岭南心血管病杂志》
2020年第1期91-97,共7页
South China Journal of Cardiovascular Diseases
基金
广东省自然科学基金项目面上项目（项目编号：2016A030313796）
广东省自然科学基金项目重点项目（项目编号：2017B030311010）
关键词
心肌病
差异表达基因
加权重共表达网络
蛋白质相互作用网络
能量代谢
cardiomyopathy
differentially-expressed genes
weighted co-expression network
protein-protein interaction network
energy metabolism
