目的 采用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)方法筛选并鉴定阿尔茨海默病(Alzheimer's disease,AD)相关的衰老基因.方法 从GEO数据库中选择GSE132903作为分析数据集,筛选AD差异表达基因(differential expressed gene,DEG),采用火山图和热图进行差异基因可视化分析;从MsigDB、Aging Altas、CellAge三个数据库中下载衰老和衰老相关基因(aging and senescence-associated gene,AS AG);WGCNA筛选与AD临床特征相关性最高的基因模块,并采用基因本体(gene ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)对模块内基因进行富集分析;取DEG、WGCNA关键模块基因及ASAG的交集基因得到AD衰老相关差异表达基因(AD age-related differential expressed gene,ARDEG),使用STRING数据库进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络分析寻找关键节点基因;使用GeneMANIA数据库分析ARDEG的共表达网络和相关功能;最后将筛选到的关键基因在已知AD患者数据库Alzdata中进行验证.结果 共筛选出226个DEG,611个ASAG,8个ARDEG.PPI筛选出排名前5位的关键基因分别为SYP、STXBP1、VAMP2、CPLX1和STX1A.Alzdata数据库验证发现除海马区VAMP2和额叶皮层STXBP1无明显改变、额叶皮层CPLX1无表达外,5个关键基因在AD其余脑区中表达均下调,且VAMP2、STXBP1和STX1A已在AD早期出现差异表达,CPLX1与Tau病理过程有关,SYP、STXBP1与β-淀粉样蛋白和Tau病理过程均有关.结论 SYP、STXBP1、VAMP2、CPLX1和STX1A均为ARDEG,有望成为AD潜在的诊断和治疗靶点.
Screening of aging key genes in Alzheimer's disease based on WGCNA
Objective Using the weighted gene co-expression network analysis(WGCNA)to explore the key genes of aging associated with Alzheimer's disease(AD).Methods GSE132903 was selected from GEO database as the analysis dataset.The differential expressed genes(DEGs)of AD were screened,and visualized with volcano and heat map.Aging and senescence-associated genes(ASAGs)were downloaded from MsigDB,Aging Altas and CellAge databases.WGCNA screened the gene modules with the highest correlation with AD,and genes of key modules subsequently performed with gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.AD age-related differential expressed genes(ARDEGs)were obtained by taking intersection genes of DEGs,key module genes of WGCNA and ASAGs.Protein-protein interaction(PPI)network analysis was performed using the STRING database to find key node genes.The co-expression networks and associated functions of key genes were analyzed using the GeneMANIA database.The key genes were validated in Alzdata database.Results 226 DEGs,606 ASAGs and 8 ARDEGs were obtained.The top 5 key genes selected by PPI were SYP,STXBP1,VAMP2,CPLX1 and STX1A.Alzdata database verified that the expressions of 5 key genes in other brain regions of AD were down-regulated,except for no significant changes of VAMP2 in hippocampus and STXBP1 in frontal cortex,as well as no expression of CPLX1 in frontal cortex.The differential expression of VAMP2,STXBP1 and STX1A appeared in the early stage of AD,and CPLX1 was related to the pathological process of Tau.SYP and STXBP1 were related to the pathological processes of amyloid β-protein and Tau.Conclusion SYP,STXBP1,VAMP2,CPLX1 and STX1A are ARDEGs,which are expected to be potential diagnostic and therapeutic targets for AD.
万方数据
维普
