炎症性肠病的基因共表达网络构建与分析

Construction and analysis of gene co-expression network of inflammatory bowel disease

目的用共表达网络的系统生物学分析炎症性肠病(Inflammatory Bowel Disease,IBD)主要包括溃疡性结肠炎(Ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)的生物学功能,为疾病机制研究和药物开发提供重要信息。方法本文以公共数据库中的212个IBD RNA-Seq数据为对象,用权重基因共表达分析(Weighted Gene Co-expression Network Analysis,WGCNA)方法构建其基因共表达网络,数据库注释、可视化和综合发现(Database for Annotation,Visualization and Integrated Discovery,DAVID)工具分析模块数据,并利用药物处理基因表达谱数据库(Connectivity map,CMAP),对可能的治疗药物进行筛选。结果 (1)共鉴定出12个具有生物学意义的共表达基因模块,模块的功能与免疫应答、血管生成、转录、翻译、能量代谢等生物学过程相关,并挖掘出每个模块的关键节点基因;(2)发现UC和CD间在胺基糖代谢、O-Glycan合成、血管生成、B细胞受体信号通路上有显著差异;(3)挖掘出12种潜在治疗药物。结论本文首次鉴定出IBD基因功能模块,这些模块可能代表疾病的主要特征,为疾病机制研究和药物开发提供重要理论依据。

Objective To analyze inflammatory bowel disease（IBD） including Ulcerative colitis（UC） and Crohn＇s disease （CD） by using the systematic biology of co-expression networks,and to provide important information for disease mechanism research and drug development. Methods A total of 212 IBD RNA＇Seq data in the public database were chosen as the study subjects. Construction of gene co-expression network was carried out by weighted gene co-expression net- work analysis （WGCNA） and the module data was analyzed by database for annotation, visualization and comprehensive discovery.The possible therapeutic drugs were screened using the drug-treated connectivity map （CMAP）. Results （1） A total of 12 biologically significant cofactor gene modules Were identified. The function of the module was related to the biological processes such as immune response, angiogenesis, transcription, translation and energy metabolism, and the key node gene of each module was excavated; （2）There were significant differences in amino acid metabolism, O-Glyean synthesis, angiogenesis, B cell receptor signaling pathway between UC and CD; （3）12 kinds of potential treatment drugs were excavated. Conclusion The IBD gene functional modules were identified for the first time. These modules may represent the main characteristics of the disease and provide important theoretical basis for disease mechanism research and drug development.