整合生物信息学与机器学习的冠心病早期诊断生物标志物筛选及中药治疗预测OA
Screening of Biomarkers for Early Diagnosis of Coronary Artery Disease and Prediction of Chinese Materia Medica Treatment by Integrating Bioinformatics and Machine Learning
目的 整合生物信息学与机器学习方法,筛选冠心病(CAD)早期诊断标志物并预测有效中药,为中医药在CAD早期防治中的应用提供依据和方法学参考.方法 本研究从GEO数据库中获取CAD患者的外周血miRNA表达数据,并利用R软件筛选出差异表达基因(DEGs).通过加权基因共表达网络分析(WGCNA)识别出高生物学意义的共表达基因模块.对DEGs与WGCNA筛选模块的共同基因进行富集分析.采用LASSO算法预测CAD的特征基因,并根据STRING数据库和蛋白-蛋白互作(PPI)网络筛选出枢纽基因,两者的共同基因被认为是潜在的生物标志物.随后在不同数据集中验证关键基因的差异表达,用受试者工作特征(ROC)曲线评估其诊断价值.通过富集分析(GSEA)识别关键基因在CAD中显著富集的通路.最后,基于关键基因,通过Coremine Medical平台预测治疗CAD的靶向中药,并结合中医理论分析其功效和性味归经.结果 本研究共鉴定出 391个DEGs,并通过WGCNA筛选出156 个基因.两者交集得到 48 个与CAD有密切关联的基因.富集分析表明,这些基因主要在过氧化物酶体增殖物激活受体(PPAR)信号通路、破骨细胞分化等通路中显著富集.通过LASSO回归等算法,筛选出水通道蛋白 9(AQP9)和 FK-506 结合蛋白5(FKBP5)作为CAD的潜在生物标志物,ROC曲线分析证实其具有较高的诊断效能(AUC>0.78).GSEA进一步揭示,AQP9 和FKBP5 在CAD中显著富集于免疫调节、代谢调控及细胞信号转导等生物学过程.最后预测出赤芍、丹参、枳实、白术等15 种治疗CAD的中药.结论 本研究通过生物信息学与机器学习技术,筛选出CAD早期诊断的生物标志物和靶向中药,为中医药早期防治CAD提供参考.
Objective To integrate bioinformatics and machine learning methods to screen biomarkers for early diagnosis of coronary artery disease(CAD)and predict effective traditional Chinese medicine(TCM),providing a basis and methodological reference for the application of TCM in the early prevention and treatment of CAD.Methods This study obtained peripheral blood miRNA expression data of CAD patients from the GEO database and used R software to screen differentially expressed genes(DEGs).Weighted gene co-expression network analysis(WGCNA)was employed to identify co-expressed gene modules with high biological significance.Enrichment analysis was performed on the overlapping genes between DEGs and the modules screened by WGCNA.The LASSO algorithm was used to predict characteristic genes of CAD,and hub genes were screened based on the STRING database and protein-protein interaction(PPI)network.The overlapping genes were considered potential biomarkers.Subsequently,the differential expression of key genes was validated in different datasets,and their diagnostic value was evaluated using receiver operating characteristic(ROC)curves.Gene set enrichment analysis(GSEA)was conducted to identify pathways significantly enriched for key genes in CAD.Finally,based on the key genes,targeted TCM for CAD treatment was predicted using the Coremine Medical platform,and their efficacy,properties,and meridian tropism were analyzed in combination with TCM theory.Results A total of 391 DEGs were identified in this study,and 156 genes were screened through WGCNA.The intersection yielded 48 genes closely associated with CAD.Enrichment analysis indicated that these genes were significantly enriched in pathways such as the peroxisome proliferator-activated receptor(PPAR)signaling pathway and osteoclast differentiation.Through algorithms such as LASSO regression,aquaporin 9(AQP9)and FK-506 binding protein 5(FKBP5)were screened as potential biomarkers for CAD,and ROC curve analysis confirmed their high diagnostic efficacy(AUC>0.78).GSEA further revealed that AQP9 and FKBP5 were significantly enriched in biological processes such as immune regulation,metabolic regulation,and cellular signal transduction in CAD.Finally,15 types of Chinese materia medica,including Chishao(Paeoniae Radix Rubra),Danshen(Salviae Miltiorrhizae Radix et Rhizoma),Zhishi(Aurantii Fructus Immaturus),and Baizhu(Atractylodis Macrocephalae Rhizoma),were predicted for the treatment of CAD.Conclusion This study utilized bioinformatics and machine learning techniques to screen biomarkers for early diagnosis of CAD and targeted Chinese materia medica,providing a reference for the early prevention and treatment of CAD with TCM.
于佳田;周聪慧;佟旭
中国中医科学院中医基础理论研究所,北京 100700南京中医药大学第三临床医学院,南京 210023中国中医科学院中医基础理论研究所,北京 100700
医药卫生
冠心病早期诊断生物标志物机器学习生物信息学中药预测
Coronary artery diseaseEarly diagnosisBiomarkersMachine learningBioinformaticsChinese materia medica prediction
《中国中医基础医学杂志》 2026 (3)
510-517,8
国家自然科学基金项目(82305439)中国中医科学院基本科研业务费优秀青年科技人才培养专项(ZZ16-YQ-053)中央级公益性科研院所基本科研业务费专项(YZX-202422)
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