脊髓损伤机制研究的生物信息学分析  

Bioinformatics Analysis of Spinal Cord Injury Mechanism Research

作　　者：任恩惠 张广智 贺学岗 高一诚 杨风光 杨亮 马占军[1,2] 解琪琪 汪静[1,2] 康学文[1,2] REN En-hui;ZHANG Guang-zhi;HE Xue-gang;GAO Yi-cheng;YANG Feng-guang;YANG Liang;MA Zhan-jun;XIE Qi-qi;WANG Jing;KANG Xue-wen(Department of Orthopaedics,Second Hospital of Lanzhou University,Lanzhou 730000,Gansu,China;The Second Clinical Medical College of Lanzhou University,Lanzhou 730000,Gansu,China)

机构地区：[1]兰州大学第二医院骨科,中国甘肃兰州730000 [2]兰州大学第二临床医学院,中国甘肃兰州730000

出　　处：《生命科学研究》2019年第6期452-461,共10页Life Science Research

基　　金：脊柱疾患疼痛机制研究及治疗甘肃省国际科技合作基地项目(甘科外[2017]2号-34);国家自然科学基金资助项目(81371230)

摘　　要：用生物信息学方法筛选参与脊髓损伤(spinal cord injury, SCI)发展过程的关键分子和通路,可为脊髓损伤发展机制的研究提供指导。从GEO数据库下载基因芯片数据,并将数据集中的样本分为脊髓损伤组(SCI组)和正常组(normal组)。应用R语言处理来自不同数据集样本间的批次效应,同时对基因芯片的表达数据进行标准化处理,并通过PCA分析监测标准化处理后数据的质量。应用R语言中的limma包分析标准化后的基因表达矩阵,以得到差异基因。将差异基因导入DAVID数据库进行GO (gene ontology)分析,并通过KEGG数据库进行通路分析。然后应用STRING数据库构建PPI网络,并通过Cytoscape中的cytoHubba插件分析得到10个hub基因。最后应用箱式图监测hub基因在不同样本中的表达,并用GeneCards数据库查询hub基因的功能。此外,为了补充差异基因筛选的不足,通过R语言对基因表达矩阵进行了GSEA (gene set enrichment analysis)分析。结果显示:TYROBP、ITGB2、PTPRC和FCER1G等基因在脊髓损伤发展过程中发挥重要的作用;细胞外基质的炎症反应、葡糖醛酸基转移酶活性的变化和星形胶质细胞的迁移等与脊髓损伤的发展机制关系密切;TNF信号通路、NF-κB信号通路和p53信号通路在脊髓损伤的发展机制中发挥重要的作用。这些关键的分子和通路在脊髓损伤中的作用值得我们进行更深入的探讨。In order to provide new ideas for the study of spinal cord injury(SCI), bioinformatics methods were used to screen key genes and pathways involved in the development of SCI. The gene chip data were downloaded from the GEO database. All samples in the dataset were divided into the SCI group and the normal group. The R language was used to process batch effects from samples of different datasets, and the expression data of the gene chip were quality-controlled and standardized. The quality of the standardized processed data was detected by PCA. The differentially expressed genes were obtained by analyzing the normalized gene expression matrix by Bayesian test in the limma package in the R language. The obtained differ-ential genes were introduced into the DAVID database for GO and KEGG analyses. A protein-protein interaction(PPI) network was constructed using the STRING database, and 10 hub genes were analyzed by cytoHubba plugin in Cytoscape. The expression levels of the hub genes were monitored by boxplots, and the functions of the hub genes were obtained by querying the GeneCards database. In order to supplement the deficiency of differential gene screening, the gene expression matrix was used to perform GSEA analysis. The results showed that genes included TYROBP, ITGB2, PTPRC and FCER1 G play an important role in the development of SCI. The changes of extracellular matrix inflammation, glucuronosyltransferase activity and astrocyte migration are closely related to the development mechanism of SCI. The results also indicated that the TNF signaling pathway, NF-κB signaling pathway and p53 signaling pathway play an important role in the development of SCI. The roles of these key genes and pathways in SCI are worthy of a more in-depth discussion.

关 键 词：脊髓损伤(SCI) 基因芯片 生物信息学 差异表达基因 

分 类 号：Q781[生物学—分子生物学] R744.9[医药卫生—神经病学与精神病学]