基于KEGG通路和基因互作网络对溃疡性结肠炎药靶基因的筛选  

Screening Target Genes for Ulcerative Colitis Based on KEGG Pathway and Gene Interaction Network

作　　者：赵秋枫[1] 王实[2] 姜洋[3] 李非[4] 罗灵和[1] 夏亮[1] 徐平珍[1] 

机构地区：[1]浙江省中医药研究院,浙江杭州310007 [2]浙江省肿瘤医院,浙江杭州310022 [3]杭州致远医学检验所有限公司,浙江杭州310009 [4]中国人民解放军军事医学科学院,北京100071

出　　处：《中华中医药学刊》2016年第11期2681-2684,I0004,I0005,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：浙江省科技计划项目(2014C33209)

摘　　要：目的:筛选与溃疡性结肠炎(ulcerative colitis,UC)相关的药靶基因,利用DAVID通路数据库和基因互做网络分析目标基因的分布和功能,促进UC的研究和新药靶点开发。方法:以ulcerative colitis检索NCBI gene数据库,提取UC相关基因数据,用DAVID分析工具提取基因富集的通路数据。对103个非冗余基因所显著富集的9条KEGG通路进行了分析,同时对富集通路中的基因同HPRD人类蛋白互作网络进行匹配。建立通路中关键基因的基因互做网络。并对所建立的相关子网进行比较,筛选和UC相关的药靶基因。结果:CD40、FAS、TNF、CD86、HLA-DRA、IL2和IL10等20个UC相关基因需要完善研究,AKT1和TNFRSF1A两个基因可能是UC治疗药物间接作用的重要靶点。结论 UC发病与细胞因子-受体相互作用通路、Ig A生产肠道免疫网络等多个通路相关。其中免疫相关通路是UC发病机制中的重要信号传导通路。CD40、FAS、TNF、CD86、HLA-DRA、IL2和IL10等20个UC相关基因在病理和治疗中都占有重要的地位。通过分析疾病相关基因的代谢通路和互作网络,有助于了解疾病的分子病理基础,并为新药设计提供可靠靶点。Objective： To screen the drug target genes associated with colitis ulcerative （UC）. We analyzed the dis- tribution and function of target genes by DAVID pathway database and gene interaction network to serve for UC drug de- signing and genetic studying. Methods ： Colitis ulcer was used to retrieve the gene data from NCBI database. Extraction of gene enriched pathway data using DAVID analysis tool. Nine KEGG pathways which had enriched 103 non redundant genes were analyzed and the genes enriched in the pathway were matched with the gene interaction network in HPRD da- tabase. Construct a network with the key genes in the pathway and make comparisons between the subnetworks to screen the target genes related to UC. Results： Twenty genes （ CD40, FAS, TNF, CD86, HLA - DRA, IL2 and IL10） were claimed for further research through our analysis. AKT1 and TNFRSF1A two genes may be the important drug targets for UC treatment. Conclusion. The pathogenesis of UC was associated with multiple pathways such as Cytokine - cytokine re- ceptor interaction,intestinal immune network for IgA production and so on. The immune related pathway was an important signaling pathway in the pathogenesis of UC. We also concluded that CD40, FAS, TNF, CD86, HLA -DRA, IL2 and IL10 played important roles in UC pathophysiology and treatment. Through gene interaction network and pathway analysis of disease associated genes,we claimed that it can help to understand the molecular basis of diseases and provide potential targets for drug development.

关 键 词：溃疡性结肠炎 基因互做网络 KEGG通路 药物靶点 

分 类 号：R574.62[医药卫生—消化系统]