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利用生物信息学方法预测潜在的强直性脊柱炎相关基因。

Predicting the potential ankylosing spondylitis-related genes utilizing bioinformatics approaches.

作者信息

Zhao Hao, Wang Dan, Fu Deyu, Xue Luan

机构信息

Department of Arthritis Emergency, Guanghua Integrative Medicine Hospital, Changning District, Shanghai, China,

出版信息

Rheumatol Int. 2015 Jun;35(6):973-9. doi: 10.1007/s00296-014-3178-9. Epub 2014 Nov 29.

Abstract

Given that ankylosing spondylitis (AS) occurs in approximately 5 out of 1,000 adults of European descent and the unclear pathogenesis, the aim of the research was to further predict the molecular mechanism of this disease. The Affymetrix chip data GSE25101 were available from Gene Expression Omnibus database. First of all, differentially expressed genes (DEGs) were identified by Limma package in R. Moreover, DAVID was used to perform gene set enrichment analysis of DEGs. In addition, miRanda, miRDB, miRWalk, RNA22 and TargetScan were applied to predict microRNA-target associations. Meanwhile, STRING 9.0 was utilized to collect protein-protein interactions (PPIs) with confidence score >0.4. Then, the PPI networks for up- and down-regulated genes were constructed, and the clustering analysis was undergone using ClusterONE. Finally, protein-domain enrichment analysis of modules was conducted using DAVID. Total 145 DEGs were identified, including 103 up-regulated and 42 down-regulated genes. These DEGs were significantly enriched in phosphorylation (p = 1.21E-05) and positive regulation of gene expression (p = 1.25E-03). Furthermore, one module was screened out from the up-regulated network, which contained 39 nodes and 205 edges. Moreover, the nodes in the module were significantly enriched in ribosomal protein (RPL17, ribosomal protein L17 and MRPL22, mitochondrial ribosomal protein L22) and proteasome (PSMA6, proteasome subunit, alpha type 6, PSMA4)-related domains. Our findings that might explore the potential pathogenesis of AS and RPL17, MRPL22, PSMA6 and PSMA4 have the potential to be the biomarkers for the disease.

摘要

鉴于强直性脊柱炎(AS)在每1000名欧洲裔成年人中约有5人发病且发病机制不明,本研究的目的是进一步预测该疾病的分子机制。Affymetrix芯片数据GSE25101可从基因表达综合数据库获取。首先,使用R语言中的Limma软件包识别差异表达基因(DEG)。此外,利用DAVID对DEG进行基因集富集分析。另外,应用miRanda、miRDB、miRWalk、RNA22和TargetScan预测微小RNA-靶标关联。同时,使用STRING 9.0收集置信度得分>0.4的蛋白质-蛋白质相互作用(PPI)。然后,构建上调和下调基因的PPI网络,并使用ClusterONE进行聚类分析。最后,使用DAVID对模块进行蛋白质结构域富集分析。共鉴定出145个DEG,包括103个上调基因和42个下调基因。这些DEG在磷酸化(p = 1.21E-05)和基因表达的正调控(p = 1.25E-03)方面显著富集。此外,从上调网络中筛选出一个模块,该模块包含39个节点和205条边。而且,该模块中的节点在核糖体蛋白(RPL17,核糖体蛋白L17和MRPL22,线粒体核糖体蛋白L22)和蛋白酶体(PSMA6,蛋白酶体亚基,α型6,PSMA4)相关结构域中显著富集。我们的研究结果可能有助于探索AS的潜在发病机制,并且RPL17、MRPL22、PSMA6和PSMA4有可能成为该疾病的生物标志物。

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