通过加权基因共表达网络分析鉴定主动脉瓣钙化的关键基因和富集通路  

Identification of key genes and enrichment pathways for aortic valve calcification through weighted gene co-expression network analysis

作　　者：张亚龙 郭盛兰[1] 覃诗耘[1] 周桂花 李雪琴 程泽 ZHANG Yalong;GUO Shenglan;QIN Shiyun;ZHOU Guihua;LI Xueqin;CHENG Ze(Department of Ultrasound,The First Affiliated Hospital of Guangxi Medical University,Nanning,530021,China)

机构地区：[1]广西医科大学第一附属医院超声科,南宁530021

出　　处：《临床心血管病杂志》2021年第6期569-575,共7页Journal of Clinical Cardiology

摘　　要：目的:筛选主动脉瓣钙化疾病(CAVD)潜在的高风险致病基因及富集通路,为CAVD的发病机制提供理论依据。方法:从高通量基因表达(GEO)数据库中下载GSE83453数据集,首先利用R语言中的limma包筛选出差异表达基因,然后再利用WGCNA包对共表达基因进行分析并筛选出与临床表型相关度高的模块基因,两者的共同致病基因被筛选出并导入STRING数据库中进行蛋白-蛋白网络互作分析,最后导入Cytoscape中筛选出关键基因。绘制差异表达基因的火山图及热图,从而更直观地展示它们之间的差异。同时,利用R语言中的ClusterProfiler包对筛选出的基因进行基因本体论分析(GO)及京都基因与基因组百科全书分析(KEGG)。结果:采用WGCNA方法从GSE83453数据集中识别出14个模块,其中浅蓝色模块的相关性系数最高(Cor=0.94,P<0.01)。最终纳入66个高风险致病基因。通过蛋白质相互作用网络分析获得66个基因及104个互作关系,从中筛选出与CAVD相关的致病基因,提示CAVD可能与细胞外基质组织、主动脉瓣间质细胞(AVICs)及炎症相关。结论:通过对CAVD患者的高通量数据集进行分析,筛选出66个高致病风险基因,再通过Cytoscape最终确定了10个关键基因,其中Ⅲ型胶原(COL3A1)、Ⅰ型胶原(COL1A1)和分泌性磷酸蛋白1(SPP1)与CAVD的形成高度相关。Objective:To screen the potential high-risk pathogenic genes and enrichment pathways of aortic valve calcification disease(CAVD)to provide a theoretical basis for the pathogenesis of CAVD.Methods:The GSE83453 data set was downloaded from the Gene Expression Omnibus(GEO)database.First,we used the limma package in the R language to screen out differentially-expressed genes(DEGs).We then used the WGCNA package to analyze the co-expressed genes and screen out the modules with high clinical phenotype correlation genes The common pathogenic genes of the two were screened by us and imported into the STRING database for protein-protein network interaction analysis,and finally imported into Cytoscape to screen out key genes.We drew volcano maps and heat maps of DEGs to show the differences more intuitively.At the same time,we used the ClusterProfiler package in the R language to perform gene ontology analysis(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis on the selected genes.Results:The WGCNA method identified 14 modules from the GSE83453 data set,among which the light blue module had the highest correlation coefficient(Cor=0.94,P<0.01).In total,66 high-risk pathogenic genes were included.Through protein interaction network analysis,66 genes and 104 interaction relationships were obtained.Furthermore,pathogenic genes related to CAVD were screened out,suggesting that CAVD may be related to extracellular matrix tissue,aortic valve interstitial cells and inflammation.Conclusion:This study analyses the high-throughput data set of CAVD patients and screened out 66 high-risk genes,and finally determined 10 key genes through Cytoscape,among which typeⅢcollagen(COL3 A1),typeⅠcollagen(COL1 A1),and secreted phosphoprotein 1(SPP1)are highly related to the formation of CAVD.It provides new ideas for further research on CAVD in the future.

关 键 词：主动脉瓣钙化疾病 加权基因共表达 差异表达基因 蛋白质互作网络 

分 类 号：R542.5[医药卫生—心血管疾病]