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中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (12): 912-927.DOI: 10.5246/jcps.2022.12.077

• 【研究论文】 • 上一篇    下一篇

整合生物信息学鉴定与分析急性心肌梗死的特征基因及潜在中药预测

姚昆鹏1,2, 张道平1,2, 刘起立1,2, 蔡虎志2, 陈青扬2,*(), 陈新宇1,2,*()   

  1. 1. 湖南中医药大学, 湖南 长沙 410208
    2. 湖南中医药大学第一附属医院, 湖南 长沙 410007
  • 收稿日期:2022-03-23 修回日期:2022-03-28 接受日期:2022-06-27 出版日期:2022-12-27 发布日期:2022-12-27
  • 通讯作者: 陈青扬, 陈新宇
  • 作者简介:
    + Tel.: +86-13807312410, E-mail:
    + Tel.: +86-18711029702, E-mail:
  • 基金资助:
    National Natural Science Foundation of China (Grant No. 81704061, 81173213), R&D plan for key areas of Hunan Provincial Department of Science and Technology (Grant No. 2019SK2321), Hunan Science and Technology Talent Lifting Project (Grant No. 2020TJ-N01), Hunan Development and Reform Commission Innovation Guidance Project (Hunan Development and Reform Investment 2019-412), Special Project for the Construction of "Four Seasons Adjusting Yang" Key Laboratory of Mental Diseases in Hunan Provincial Administration of Traditional Chinese Medicine, the "Double First-Class" Discipline Construction Project of Traditional Chinese Medicine in Hunan Province.

Integrating bioinformatics to identify and analyze feature genes of acute myocardial infarction and potential Chinese medicine prediction

Kunpeng Yao1,2, Daoping Zhang1,2, Qili Liu1,2, Huzhi Cai2, Qingyang Chen2,*(), Xinyu Chen1,2,*()   

  1. 1 Hunan University of Chinese Medicine, Changsha 410208, Hunan, China
    2 The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan, China
  • Received:2022-03-23 Revised:2022-03-28 Accepted:2022-06-27 Online:2022-12-27 Published:2022-12-27
  • Contact: Qingyang Chen, Xinyu Chen

摘要:

采用Gene Expression Omnibus (GEO)数据集联合机器学习研究急性心肌梗死(acute myocardial infarction, AMI)的差异基因, 并预测具有调控作用的潜在成分及中药。从GEO数据库下载AMI的人类全基因组数据集(GSE66360和GSE61145), 以GSE66360作为测试集, 通过R语言的normalize Between Arrays包进行校正后, 再调用limma包获取差异基因(DEGs), 对DEGs作Gene Ontology (GO)、Kyoto Encyclopedia of Genes and Genomes (KEGG)、Disease Ontology (DO)富集分析; 采用SVM及随机森林树法筛选特征基因, 利用GSE61145数据集对得出的特征基因进行验证; 通过CTD数据库找到AMI特征基因所对应的中药成分, 利用Coremine数据库映射中药成分所对应的中药, 并依据《中药大辞典》、《中华本草》、《中国药典》等对所得中药的频次、四气、五味、归经进行汇总。通过对GSE66360数据集进行分析, 得到317个差异基因, 其中306个上调, 11个下调, GO和KEGG富集分析显示AMI的差异基因主要涉及中性粒细胞介导的炎症和免疫反应、脂代谢异常、脂质和动脉粥样硬化相关通路等, DO富集分析表明差异基因与动脉硬化性心血管疾病、肺部疾患等密切相关。通过SVM及随机森林树法得到6个特征基因: ZFP36、GADD45A、PELI1、METRNL、MMP9、CXCL16。CTD映射到成分97种, Coremine数据库映射到中药824味, 汇总后发现治疗AMI的中药以甘、苦、温为主, 多归于脾、胃、肝经。经汇总后, 调控AMI的特征基因(ZFP36、GADD45A、PELI1、METRNL、MMP9、CXCL16)成分主要有苯并[a]芘, 四氯二苯二氧芑, 对乙酰氨基酚等, 中药有茶树根、郁金、人参等, 其性味为甘、苦、温, 归经多为脾、胃、肝经。

关键词: 急性心肌梗死, GEO, 中药, 生物信息学

Abstract:

In the present study, the Gene Expression Omnibus (GEO) dataset combined with machine learning was used to study differential genes in acute myocardial infarction (AMI) and to predict potential components and herbal medicines with regulatory effects. The human genome datasets of AMI (GSE66360 and GSE61145) were downloaded from the GEO database, and GSE66360 was used as the test set. After correction by normalization Between Arrays package of R, the limma package was used to obtain differentially expressed genes (DEGs). Then, we carried out Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analysis of DEGs. The feature genes were screened by SVM and random forest tree method, and the obtained feature genes were verified by the GSE61145 dataset. The components of traditional Chinese medicine (TCM) corresponding to AMI feature genes were found by the CTD database, and the corresponding TCM components were mapped by the Coremine database. According to the Dictionary of Traditional Chinese Medicine, Chinese Materia Medica, and Chinese Pharmacopoeia, the frequency, the four qi, five flavors, and meridian tropism of the obtained TCM were summarized. Through the analysis of the GSE66360 dataset, 317 DEGs were obtained, of which 306 were up-regulated, and 11 were down-regulated. GO and KEGG enrichment analyses showed that the DEGs of AMI were mainly involved in neutrophil-mediated inflammation and immune response, abnormal lipid metabolism, lipid, and atherosclerosis-related pathways. DO enrichment analysis showed that the DEGs were closely related to atherosclerotic cardiovascular diseases and lung diseases. Six feature genes were obtained by SVM and random forest tree method, including ZFP36, GADD45A, PELI1, METRNL, MMP9, and CXCL16. Moreover, we found that the treatment of AMI Chinese medicine to sweet, bitter, and warm mostly attributed to the spleen, stomach, and liver. Besides, the components corresponding to the feature genes regulating AMI (ZFP36, GADD45A, PELI1, METRNL, MMP9, CXCL16) mainly included benzo(a)pyrene, tetrachlorodibenzodioxin, acetaminophen, and so on, and the corresponding TCMs included Camellia sinensis, Curcumaaromatica Salisb, Panax ginseng, and so on. In addition, a sweet taste, bitter taste, warm taste, and channel entry mainly belonged to the spleen, stomach, and liver meridians.

Key words: Acute myocardial infarction, GEO, Traditional Chinese medicine, Bioinformatics

Supporting: