文章摘要
陈盛,王高华.基于生物信息学方法对抑郁症小鼠脑组织差异基因表达的分析[J].神经损伤功能重建,2021,16(3):125-129
基于生物信息学方法对抑郁症小鼠脑组织差异基因表达的分析
Differential Gene Expression in Brain Tissues of Depressed Mice Based on BioinformaticsAnalysis
  
DOI:
中文关键词: 生物信息学  抑郁症  GEO数据库  海马  杏仁核
英文关键词: bioinformatics  depression  GEO database  hippocampus  amygdala
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作者单位
陈盛,王高华 武汉大学人民医 院 精 神 卫 生 中 心/武 汉 大 学 人 民医院神经精神 病研究所 
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中文摘要:
      目的:基于生物信息学方法分析抑郁症小鼠海马和杏仁核等脑组织中差异表达基因及其可能的生物学 功能。方法:选取GEO数据库中数据集GSE151807,利用R软件及Limma包进行差异基因的筛选;对数据集 GSE151807基因表达矩阵进行基因集富集分析;利用David在线分析工具对差异基因进行基因本体论(GO) 富集分析和KEGG信号通路富集分析。利用String在线网站构建差异基因表达蛋白间相互作用网络(PPI), 使用Cytoscape软件进行模块聚类和关键基因筛选及数据可视化。结果:抑郁症小鼠脑组织(海马和杏仁核) 中共有351个基因表达水平发生改变,其中182个基因上调,169个基因下调。对基因表达矩阵进行基因集富 集分析发现,神经活性配体-受体相互作用、泛素介导的蛋白水解、亨廷顿氏病、谷胱甘肽代谢、过氧化物酶、 长期抑郁等有关的基因显著富集。差异基因GO富集分析发现,RNA聚合酶Ⅱ启动子转录的调控、细胞内膜 结合细胞器、转录因子活性调控等显著富集。差异基因KEGG信号通路富集分析发现,烟酸酯和烟酰胺代 谢、孕激素介导的卵母细胞成熟、ECM-受体相互作用等信号通路显著富集。通过构建蛋白质相互作用网络, 筛选出2个核心基因Fos和Itpkb,其中Fos基因在抑郁症小鼠海马和杏仁核组织中为下调基因,而Itpkb基因 则为上调基因。结论:抑郁症小鼠脑组织(海马和杏仁核)中基因表达发生显著改变,差异基因参与不同的生 物学过程和信号通路,Fos和Itpkb可能是与抑郁症发生相关的核心基因,可能作为潜在的药物治疗靶点。
英文摘要:
      To analyze the differentially expressed genes and their possible biological function in the brain tissues (hippocampus and amygdala) of depressed mice based on bioinformatics methods. Methods: Data set GSE151807 in the GEO database was selected, and the R software and Limma package were used to screen differentially expressed genes. Gene set enrichment analysis was carried out on the expression matrix of data set GSE151807. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis were performed on the differentially expressed genes using the David (Database for Annotation, Visualization, and Integrated Discovery) online tool. The String website was used to construct a protein-protein interaction network (PPI) of the differentially expressed genes. The Cytoscape software was used for module clustering, key gene screening, and data visualization. Results: The expression levels of 351 genes in the brain tissues (hippocampus and amygdala) of depressed mice showed change; 182 genes were up-regulated and 169 down-regulated. Gene set enrichment analysis of the gene expression matrix showed that genes related with the neuroactive ligand-receptor interaction, ubiquitin-mediated proteolysis, Huntington's disease, glutathione metabolism, peroxidase, and long-term depression were significantly enriched. GO enrichment analysis showed that regulation of transcription from the RNA polymerase II promoter, intracellular membrane-bounded organelles, and transcription factor activity regulation were significantly enriched. KEGG pathway enrichment analysis revealed that nicotinate and nicotinamide metabolism, progesterone-mediated oocyte maturation, and ECM-receptor interaction were significantly enriched. Through construction of the protein interaction network, two hub genes Fos and Itpkb were selected. Fos gene is a down-regulated gene in the hippocampus and amygdala tissue of depressed mice while Itpkb gene is an up-regulated gene. Conclusion: Gene expression in the brain tissues (hippocampus and amygdala) of depressed mice is significantly changed. Differentially expressed genes are involved in different biological processes and signaling pathways. Fos and Itpkb may be key genes related to depression and may be used as potential targets of anti-depression drugs.
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