摘要
目的 筛选阿尔茨海默病(Alzheimer’s Disease,AD)核心基因并对其进行功能分析,为确定早期诊断标志物提供参考依据。方法 从公共数据平台NCBI-GEO DataSets中下载基因芯片数据集GSE5281,使用R/Bioconductor统计语言筛选出与AD相关的差异表达基因(DEGs);使用DAVID 6.8生物信息学资源数据库进行GO功能注释和KEGG通路富集分析;使用STRING数据库和Cytoscape 3.8.2软件进行蛋白质-蛋白质相互作用(PPT)网络分析。结果 筛选出DEGs共1037个,其中上调312个,下调725个。DEGs编码蛋白的PPI网络含节点979个,边596条;CytoHubba插件MCC法构建模块筛选出10个候选关键基因,GO分析结果显示,主要富集于线粒体电子传递NADH到泛醌、线粒体呼吸链复合体Ⅰ组装、线粒体电子传递泛醌到细胞色素c等7个生物过程;主要富集于线粒体内膜、呼吸链复合体Ⅰ,呼吸链复合体Ⅲ等7个细胞成分;主要富集于NADH脱氢酶(泛醌)活性、泛醌-细胞色素-C还原酶活性、NADH脱氢酶活性等9个分子功能;主要富集在氧化磷酸化(hsa00190)、代谢途径(hsa01100)、帕金森病(hsa05012)、阿尔茨海默病(hsa05010)等7条信号通路。其中枢纽基因(Hub基因)为NDUFAB1、UQCRC2、UQCRC1。结论 关键核心基因为NDUFAB1、UQCRC2、UQCRC1,可能是AD发生发展的潜在靶点。
Objective To screen the core genes of Alzheimer’s disease(AD)and analyze their functions,so as to provide reference for identifying early diagnostic markers of AD.Methods Gene chip dataset GSE5281 was downloaded from public data platform NCBI-GEO DataSets.R/Bioconductor statistical language was used to screen out differential expression genes(DEGs)related to AD.Bioinformatics resource database DAVID 6.8 was employed for GO functional annotation and KEGG pathway enrichment analysis.Database STRING and software Cytoscape 3.8.2 was used for network analysis of protein-protein interaction(PPT).Results A total of 1037 DEGs were screened out,among which 312 were up-regulated and 725 down-regulated.The PPI network of DEGs encoded proteins contained 979 nodes and 596 edges.CytoHubba plug-in MCC method was adopted to construct the module to screen out 10 candidate key genes.GO analysis showed that they were mainly enriched in seven biological processes,including mitochondrial electron’s transference of NADH to ubiquinone,assembly of mitochondrial respiratory chain complex I,and mitochondrial electron’s transferance of ubiquinone to cytochromec;in seven cell components,such as mitochondrial inner membrane,mitochondrial respiratory chain complexⅠandⅢ.They were also enriched in nine molecular functions,such as the activity of NADH dehydrogenase(ubiquinone),activity of ubiquinone-cytochrome C reductase,NADH dehydrogenase activity;in 7 signaling pathways,including oxidative phosphorylation(hsa00190),metabolic pathway(hsa01100),Parkinson’s disease(hsa05012),Alzheimer’s disease(hsa05010),among which the Hub genes were NDUFAB1,UQCRC2,and UQCRC1.Conclusion The key core genes are NDUFAB1,UQCRC2,and UQCRC1,which may be the potential targets for the development of AD.
作者
李莎莎
王琦
钟斌
陈依烛
陈佳音
凌雁武
Li Shasha;Wang Qi;Zhong Bin;Chen Yizhu;Chen Jiayin;Ling Yanwu(Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;The Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China)
出处
《右江民族医学院学报》
2021年第6期746-750,756,共6页
Journal of Youjiang Medical University for Nationalities
基金
国家自然科学基金项目(31560294,30960155)。
关键词
阿尔茨海默病
差异基因
生物信息学
Alzheimer’s disease
differential genes
bioinformatics