胆道闭锁差异基因表达谱挖掘和生物信息学分析  

Detection and bioinformatics analysis of differential expressed genes in biliary atresia

作　　者：陈国铭 黄楚瑶 陈腾宇 綦向军 梁妙珍 张洁 刘韵韵 鲁嘉欣 吕慧页 许华[3] CHEN Guo-ming;HUANG Chu-yao;CHEN Teng-yu;QI Xiang-jun;LIANG Miao-zhen;ZHANG Jie;LIU Yun-yun;Lü Jia-xin;LU Hui-ye;XU Hua(Department of Pediatries,The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;Clinical Medical College of Acupuncture,Moxibustion,and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;Department of Pediatries,the First Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China)

机构地区：[1]广州中医药大学第一临床医学院儿科,广东广州510405 [2]广州中医药大学针灸康复临床医学院,广东广州510405 [3]广州中医药大学第一附属医院儿科,广东广州510405

出　　处：《中国临床药理学杂志》2020年第7期863-865,869,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81373686)。

摘　　要：目的通过生物信息学方法挖掘胆道闭锁(BA)的关键差异基因,并进一步探究其发病机制。方法从基因表达综合数据库(GEO)中下载胆道闭锁相关基因芯片数据集,并用GEO2R分析工具筛选出正常组织与BA的差异表达基因。通过DAVID V6.8数据库富集分析BA差异基因的生物学过程、细胞组分、分子功能以及信号通路,以探讨BA发病过程中差异表达基因主要涉及的生理病理机制。用STRING V10.5数据库构建蛋白-蛋白相互作用(PPI)网络以分析差异表达蛋白之间的相互作用关系。结果经筛选后发现胆道闭锁基因测序集GSE46960包含103个差异表达基因,其中有65个为上调基因,38个下调基因。基因本体(GO)富集分析表明:BA差异表达基因主要涉及细胞对氨基酸刺激的反应、正向调控趋化单核细胞、细胞黏附、氧化还原过程和急性时相反应等生物过程;分子功能主要参与细胞外基质的结构组成以及RNA聚合酶Ⅱ核心启动子的转录因子活性,参与氧化还原酶反应;细胞成分涉及细胞外基质、顶端质膜、高密度脂蛋白粒子等。经基因和基因组的京都百科全书数据库(KEGG)富集的差异表达基因信号通路包括Toll样受体信号通路、肿瘤坏死因子信号通路、磷脂酰肌醇激酶3-蛋白激酶B信号通路和代谢通路。PPI网络图显示BA的关键致病基因包括乙醛氧化酶1、Ⅲ型胶原α1、胰岛素样生长因子-1等。结论生物信息学可以有效筛选与预测BA的关键差异基因和发病机制,其中部分结果已得到实验证实,验证了该方法的正确性,未经实验证实的差异基因可能是BA发病机制中新的研究靶点。Objective To screen the key differently expressed gene of biliary atresia(BA) by bioinformatics analysis for further study of predicted gene targets.Methods Gene data sets were downloaded from the Gene Expression Omnibus(GEO) database and differential expression genes of normal tissue and BA were screened via GEO2 R analysis tool.To explore the main mechanism involved in the differentially expressed genes in the pathogenesis of BA, DAVID V6.8 database was used to enrich the biological process, cellular component, molecular function and signal pathway of the differentially expressed genes.To investigate the functional relationship between differentially expressed target proteins, we constructed the protein-protein interaction(PPI) network to analyze the key genes with STRING V10.5.Results After screening, it was found that the dataset GSE46960 contained 103 differentially expressed genes, among which 65 were up-regulated and 38 were down-regulated.Gene ontology(GO) enrichment analysis showed that differentially expressed genes of BA mainly affected the biological processes such as cellular response to amino acid stimulu,positive regulation of monocyte chemotaxis,cell adhesion,oxidation-reduction process and acute-phase response.The enriched molecular function was mainly involved in extracellular matrix structural constituent and transcription factor activity,RNA polymerase Ⅱ core promoter proximal region,etc,while participate in the composition of extracellular matrix,high-density lipoprotein particle and apical plasma membrane.The differentially expressed gene signal pathways enriched by Kyoto Encyclopedia of Genes and Genomes(KEGG),and included Toll-like receptor signal pathway,tumor necrosis factor signal pathway,phosphatidylinositol kinase 3-protein kinase B signal pathway and metabolic pathway.PPI showed that the key pathogenic genes of BA included aldehyde oxidase 1(AOX1),collagen alpha-1(Ⅲ) chain(COL3 A1),insulin-like growth factor I(IGF-1),etc.Conclusion Bioinformatics can effectively predict the key d

关 键 词：胆道闭锁 生物信息学 差异基因 数据挖掘 

分 类 号：R97[医药卫生—药品]