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通过基因表达谱分析探索炎症性肠病的关键基因。

Crucial genes of inflammatory bowel diseases explored by gene expression profiling analysis.

作者信息

Xie Dehong, Zhang Yudong, Qu Hao

机构信息

a Department of General Surgery , Beijing Chao-Yang Hospital, Capital University of Medical Sciences , Beijing , China.

出版信息

Scand J Gastroenterol. 2018 Jun;53(6):685-691. doi: 10.1080/00365521.2018.1461923. Epub 2018 Jun 16.

DOI:10.1080/00365521.2018.1461923
PMID:29909694
Abstract

OBJECTIVES

This study aimed to uncover new potential genes associated with the inflammatory bowel diseases (IBDs).

MATERIALS AND METHODS

The datasets GSE36807 and GSE9686 were obtained from Gene Expression Omnibus (GEO). Totally, 24 Crohn's disease (CD) samples, 20 ulcerative colitis (UC) samples and 15 healthy controls in the two datasets were used for our analysis. The differentially expressed genes (DEGs) were identified by limma package. Then, co-expression network was constructed by weighted gene correlation network analysis (WGCNA) package, and co-expression network modules were obtained via clustering method. The top 100 genes with the highest connectivity degrees were selected to construct a new co-expression network (CEN). Besides, pathway enrichment analysis for the genes in identified modules was conducted with the clusterProfiler package in R.

RESULTS

Totally, 302 and 2276 DEGs were respectively identified in CD and UC samples, and 291 ones were both differentially expressed in the two subtypes. Five modules were identified from the CEN. In the new CEN consisted of the top 100 genes with the highest connectivity degrees, the up-regulated DEGs all belonged to module 5, and the down-regulated ones all belonged to module 1. Furthermore, pathway enrichment analysis showed that some DEGs were related to primary immunodeficiency (e.g., CD4, CD3D and CD40LG), complement and coagulation cascades (e.g., C2, C1QB and C7) and nitrogen metabolism (e.g., CA1, CA12 and CA2).

CONCLUSION

The DEGs correlated with primary immunodeficiency, complement and coagulation cascades and nitrogen metabolism might be important for the development of IBD.

摘要

目的

本研究旨在发现与炎症性肠病(IBD)相关的新的潜在基因。

材料与方法

数据集GSE36807和GSE9686来自基因表达综合数据库(GEO)。我们使用这两个数据集中的24个克罗恩病(CD)样本、20个溃疡性结肠炎(UC)样本和15个健康对照进行分析。通过limma软件包鉴定差异表达基因(DEG)。然后,使用加权基因共表达网络分析(WGCNA)软件包构建共表达网络,并通过聚类方法获得共表达网络模块。选择连接度最高的前100个基因构建新的共表达网络(CEN)。此外,使用R语言中的clusterProfiler软件包对鉴定出的模块中的基因进行通路富集分析。

结果

在CD样本和UC样本中分别鉴定出302个和2276个DEG,其中291个在两种亚型中均差异表达。从CEN中鉴定出5个模块。在由连接度最高的前100个基因组成的新CEN中,上调的DEG均属于模块5,下调的DEG均属于模块1。此外,通路富集分析表明,一些DEG与原发性免疫缺陷(如CD4、CD3D和CD40LG)、补体和凝血级联反应(如C2、C1QB和C7)以及氮代谢(如CA1、CA12和CA2)有关。

结论

与原发性免疫缺陷、补体和凝血级联反应以及氮代谢相关的DEG可能对IBD的发生发展具有重要意义。

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