基于KEGG通路和基因互作网络对充血性心力衰竭相关基因的筛选

Screen of Target Genes for Congestive Heart Failure Based on KEGG Pathway and Gene Interaction Network

关键词:  充血性心力衰竭  基因互作网络  KEGG通路  药物靶点

Key words:  congestive heart failure  gene interaction network  KEGG pathway  drug target

摘要:

目的 筛选与充血性心力衰竭（congestive heart failure，CHF）相关的药物靶点基因，利用DAVID通路数据库和基因互作网络分析目标基因的分布和功能，促进CHF的研究和新药的开发。方法 以"congestive heart failure"检索NCBI基因数据库，提取CHF相关基因数据，采用DAVID分析工具提取基因富集的通路数据。对40个非冗余基因所显著富集的11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互作网络。并对所建立的相关子网进行比较，筛选和CHF相关的药物靶点基因。结果 MMP9、LMNA、DMD、EMD、AGTR1、EDNRB、NOS3和TNF等21个CHF相关基因需要完善研究，LMNA、MMP9和AR 3个基因可能是CHF治疗药物间接作用的重要靶点。结论 CHF发病与cGMP-PKG信号通路、钙离子信号通路、扩张型心肌病、肥厚型心肌病等多个通路相关。MMP9、LMNA、DMD、EMD、AGTR1、EDNRB、NOS3和TNF等21个CHF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基础，并为新药研发提供可借鉴的思路。

Abstract:

OBJECTIVE Screening genes associated with heart failure, using the DAVID pathway database and gene network to analyze the distribution and function of the target genes, to promote the research of congestive heart failure and development of new medicine. METHODS "Congestive heart failure" was used to retrieve the gene data from NCBI database. Extraction of gene enriched pathway data by used DAVID analysis tool. Analyses were made on 11 KEGG pathways enriched by 40 non redundant genes, while genes in enrichment pathways were matched with HPRD protein interaction networks at the same time. Constructed a network with the key genes in the pathway. And made comparisons between the subnetworks to screen the target genes related to congestive heart failure(CHF). RESULTS Twenty-one genes(MMP9, LMNA, DMD, EMD, AGTR1, EDNRB, NOS3 and TNF, et al) were claimed for further research. LMNA, MMP9 and AR three genes might be the important drug targets for the indirect action of CHF therapeutic drugs. CONCLUSION The pathogenesis of CHF is associated with multiple pathways such as cGMP-PKG signaling pathway, calcium signaling pathway, dilated cardiomyopathy pathway, hypertrophic cardiomyopathy pathway and so on. Twenty-one genes(MMP9, LMNA, DMD, EMD, AGTR1, EDNRB, NOS3 and TNF, et al) play important roles in CHF pathophysiology and treatment. Through gene interaction network and pathway analysis of disease associated genes, which can help to understand the molecular basis of diseases and provide a reference for new drug research and development.