中国医院用药评价与分析2025，Vol.25Issue(11)：1296-1302,7.DOI:10.14009/j.issn.1672-2124.2025.11.004
基于DGIdb与Finn数据库的系统性可成药全基因组预测睡眠障碍靶基因及治疗药物
Systematic Druggable Genome-Wide Prediction of Target Genes and Therapeutic Drugs for Sleep Disorder Based on DGIdb and Finn Databases
摘要
Abstract
OBJECTIVE:To explore the potential therapeutic targets and drugs for sleep disorders based on Mendelian randomization(MR)analysis of the druggable genome.METHODS:The research was carried out in three stages by using systems biology strategy.The candidate genes causally associated with sleep disorder were screened by two-sample MR,then the protein-protein interaction(PPI)network was constructed,the biological function of targets was analyzed by enrichment analysis to reveal the core signaling pathway,on that basis,the new therapeutic drugs were explored by drug enrichment analysis.The binding affinity between potential drug molecules and targets was evaluated based on molecular docking methods.RESULTS:Based on MR analysis,43 targets significantly associated with sleep disorder were screened out,among which mitogen-activated protein kinase(MAPK)3 and CDC42 showed significant association with sleep disorder phenotypes through PPI analysis.Gene ontology enrichment analysis showed that the significant druggable genes related to sleep disorder were mainly involved in the biological processes of peptide reaction,serine family amino acid biosynthesis and stress-activated MAPK cascade regulation.The Kyoto encyclopedia of genes and genomes pathway enrichment analysis indicated that differential genes were significantly enriched in functional pathways of oxytocin signaling pathway and Apelin signaling pathway.Results of drug enrichment and molecular docking further revealed that romidepsin and 5-iodo-tuberculin had excellent binding energy with five targets,which suggested that the two drugs were potential therapeutic drugs.CONCLUSIONS:MAPK3 and CDC42 are significant targets for the intervention of sleep disorder,romidepsin and 5-iodotuberculosistin are highly potential and valuable drugs for the treatment of sleep disorder.The model of this study integrates genetic evidence with computational simulation,which is expected to provide a new perspective for analyzing the mechanism of sleep disorder,with significant scientific value for the development of new targeted drugs,the optimization of present drug indications and the elucidation of pathological mechanisms,as well as provide reference for subsequent experimental verification.关键词
孟德尔随机化/可成药基因/睡眠障碍/DGIdb数据库/Finn数据库Key words
Mendelian randomization/Druggable gene/Sleep disorder/DGIdb database/Finn database分类
医药卫生引用本文复制引用
朱艳宁,杨敬言,陈晓瑶,刘慧萱,陈实,张淇范,罗斌..基于DGIdb与Finn数据库的系统性可成药全基因组预测睡眠障碍靶基因及治疗药物[J].中国医院用药评价与分析,2025,25(11):1296-1302,7.基金项目
国家中医药管理局中医药传承与创新"百千万"人才工程·第四批全国中医(临床、基础)优秀人才研修项目(No.J20184832009) （临床、基础）
