小鼠耳蜗性聋的关键通路和差异表达基因分析

Identification of Key Pathways and Genes in Mice of Cochlear Deafness using Bioinformatics Analysis

杨媛媛;黄冠江;陶源;

1:北京大学深圳医院耳鼻咽喉科

2:浙江大学医学院附属第二医院耳鼻咽喉科

摘要
目的利用基因表达数据库查找6月龄的听力正常CBA小鼠和耳蜗性聋小鼠的表达谱基因芯片的原始数据,对关键通路和差异表达基因(differentially expressed genes,DEGs)进行数据库挖掘和分析,为耳蜗性聋的治疗提供参考。方法从公共数据库基因表达数据库(gene expression omnibus,GEO)中下载小鼠耳蜗性聋表达谱相关数据集,采用R软件筛选差异表达基因并进行火山图分析,再将DEGs进行热图分析,采用David在线工具对其进行基因本体分析(gene ontology analysis,GO)、京都基因和基因组百科全书分析(kyoto encyclopedia of genes and genomes, KEGG),然后,将差异表达基因导入STRING在线数据库进行蛋白质互作网络分析(protein protein interaction network,PPI network),绘制差异表达基因互作网络图,并将互作网络数据导入Cytoscape软件中,筛选网络中心节点和关键基因,分析关键子网络。并对DEGs行基因集富集分析(gene set enrichment analysis,GSEA),筛选重要通路。结果共筛选出191个DEGs,其中表达上调的基因79个,表达下调的基因112个。在GO分析中,上调的DEGs主要参与细胞外空间、细胞外区及趋化因子受体结合等过程,下调的DEGs主要参与有丝分裂核分裂、细胞周期及细胞分裂等过程。在KEGG分析中,上调的DEGs主要参与肿瘤坏死因子信号通路,下调的DEGs主要参与细胞周期、孕酮介导的卵母细胞成熟、卵母细胞的减数分裂及p53信号通路等。PPI网络筛选出前10个关键基因:Kif11、Cdc20、Cdk1、Bub1b、Ccnb2、Cdca8、Cdca5、Sgol1、Hmmr及Ncapg。GSEA分析显示:前三位上调的通路包括树突细胞成熟、Croonquist Nras信号转导及反应金属离子硫蛋白转运,而前三位下调的通路包括半乳糖代谢、氧化磷酸化及嘌呤代谢。结论本研究得到了一个较全面的小鼠耳蜗性聋差异表达基因的生物信息学分析结果,但仍需进一步用基础实验来验证。
关键词
小鼠;耳蜗性聋;通路;基因
基金项目(Foundation):
深圳市卫生计生系统科研项目(SZXJ2018079);; 深圳市医疗卫生三名工程项目(SZSM201612076)
作者
杨媛媛;黄冠江;陶源;
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杨媛媛黄冠江陶源