小鼠胚胎期与成熟期肝脏表达谱芯片数据挖掘及生物信息学分析

Data mining and bioinformatics analysis of expression profile chip for embryonic and mature mice liver

目的深度分析小鼠胚胎期与成熟期肝脏差异表达基因。方法从美国国家生物技术信息中心(NCBI)的GEO数据库下载编号为GSE65063的基因表达谱数据,提取其中胚胎期14 d及生后56 d芯片,采用在线分析工具GEO2R完成差异表达基因(DEGs)筛选。使用DAVID对DEGs进行基因本体论及京都基因与基因组百科全书生物学通路富集分析,采用STRING分析DEGs所编码蛋白质之间的相互作用,结合CytoScape软件进行可视化;运用CytoScape软件中加载的MCODE进行功能模块构建,利用CytoHubba筛选枢纽基因并对其进行分析与构建PPI网络图。结果成熟期肝脏相对于胚胎期,共筛选出2969个DEGs,其中上调1620个,下调1349个。上调DEGs主要富集在与代谢有关的生物过程、细胞器组分及代谢路径,而下调DEGs则主要富集于细胞周期、DNA修复等与细胞增殖相关的细胞器、生物过程及信号通路。模块分析示排列首位的基因模块全部为下调基因,主要富集于与细胞周期、细胞衰老相关的信号通路。模块二主要与补体系统、胆固醇代谢及PARP信号通路有关。模块三则主要与视黄醇代谢、甾体激素合成等有关。共筛选出枢纽基因16个,其中14个表达下调,2个上调。结论肝脏成熟期与胚胎期基因表达谱有显著差异,肝脏的发育及成熟在不同时间与空间受到特定基因群调控,在成熟期肝脏,以代谢相关基因为主,在胚胎期则主要富集于细胞增殖分裂相关基因。筛选出来的枢纽基因尤其是下调基因可能作为肝脏异常如肝癌等疾病的早期诊断与判断预后的指标,具有重要临床意义。

Objective To depth analysis of liver differential expression genes in embryonic and mature mice.Methods Download gene expression profile data numbered GSE65063 from the National Center for Biotechnology Information(NCBI)GEO database,microchips were extracted at 14 embryonic days and 56 postnatal days.Online analysis tool GEO2R was used to complete differentially expressed genes(DEGs)screening.DAVID was used to analyze the gene ontology and Kyoto Encyclopedia of Genes and Genomes biological pathway enrichment of DEGs,STRING was used to analyze the interaction between proteins encoded by DEGs,visualization with Cytoscape software.MCODE loaded in Cytoscape software was used to build functional modules,CytoHubba was used to screen the hub genes and analyze them to construct PPI network map.Results A total of 2969 DEGs were screened in mature liver compared with embryonic liver,of which 1620 were up-regulated and 1349 were down-regulated.Upregulated DEGs were mainly concentrated in metabolism-related biological processes,organelle components and metabolic pathways,while down-regulated DEGs were mainly concentrated in cell cycle,DNA repair and other cell proliferation-related organelles,biological processes and signaling pathways.Modular analysis showed that the top gene modules were all down-regulated genes,which were mainly enriched in signaling pathways related to cell cycle and cell senescence.Module two was mainly related to complement system,cholesterol metabolism and PARP signaling pathway.Module third was mainly related to retinol metabolism steroid and somatic hormone synthesis.A total of 16 hub genes were screened out,among which 14 were down-regulated and two were up-regulated.Conclusion There are significant differences in gene expression profiles between matare and embryonic liver maturation and embryonic stage.Liver development and maturation are regulated by specific gene groups in different time and space.Metabolism-related genes are dominant in mature liver,while cell proliferation and division related genes are mainly concentrated in embryonic liver.The screened hub genes,especially the down-regulated genes,may be used as early diagnostic and prognostic indicators for liver abnormalities such as liver cancer,which is of great clinical significance.