通讯作者: 杨宏艳, yhycicy@163.com

DOI：10.12201/bmr.202407.00036

1. School of Pharmacy,Qiqihar Medical University,Qiqihar 161006,China2. Affiliated Third Hospital,Qiqihar Medical University,Qiqihar 161006,China

• 摘要：目的 采用加权基因共表达网络分析（Weighted gene co-expression network analysis, WGCNA）方法筛选及鉴定阿尔茨海默病（Alzheimers 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 genes，DEGs），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 Genes，ASAGs）；WGCNA筛选与AD临床特征相关性最高的基因模块，并采用基因本体论（Gene ontology, GO）、京都基因和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）对模块内基因进行富集分析；取DEGs、WGCNA关键模块基因以及ASAGs的交集基因，即AD衰老相关差异表达基因（AD age-related differential expressed genes，ARDEGs），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ARDEGs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DEGs（其中78个上调，148个下调），611个ASAGs，8个ARDEGs。PPI筛选出排名前5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无明显改变外，5个关键基因在AD其余脑区中表达均下调，且VAMP2、STXBP1和STX1A在AD早期已出现差异表达，CPLX1与Tau病理过程有关，SYP、STXBP1与Aβ和Tau病理过程均有关。结论 SYP、STXBP1、VAMP2、CPLX1和STX1A为AD衰老差异基因，有望成为AD潜在的诊断和治疗靶点。

  关键词： 阿尔茨海默病; 加权基因共表达网络分析; 衰老基因; 关键基因; 生物信息学

   

  Abstract: Objective Using the weighted gene co-expression network analysis (WGCNA) to explore the key genes of aging associated with Alzheimers 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 related 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. The key module genes were intersected with differential genes and aging genes to obtain AD age-related differential expressed genes (ARDEGs). 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 (78 up-regulated, 148 down-regulated) and 606 ASAGs were obtained. WGCNA screened out the black-gray modules with high correlation with the clinical characteristics of AD, and obtained 105 key candidate genes. The candidate gene was intersected with differential gene and aging gene to obtain 8 ARDEGs. 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 Aβ and Tau. Conclusion SYP, STXBP1, VAMP2, CPLX1 and STX1A are AD age-related differential expressed genes, which are expected to be potential diagnostic and therapeutic targets for AD.

  Key words: Alzheimers disease, Weighted gene co-expression network analysis, Aging genes, Key genes, Bioinformatics; ; ; ; 

  提交时间：2024-07-17

  版权声明：作者本人独立拥有该论文的版权，预印本系统仅拥有论文的永久保存权利。任何人未经允许不得重复使用。
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• 序号	提交日期	编号	操作
  1	2024-06-16	bmr.202407.00036V1	下载

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