心肌梗死中淋巴管新生关键差异基因的生物信息学分析及防治中药的筛选

Bioinformatics analysis of lymphangiogenesis in myocardial infarction and screening of traditional Chinese medicine for prevention treatment

关键词:  心肌梗死  淋巴管新生  生物信息学  中药

Key words:  myocardial infarction  lymphangiogenesis  bioinformatics  traditional Chinese medicine

摘要:

[目的] 通过Lasso回归与SVM-RFE算法等生物信息学方法筛选心肌梗死（MI）中与淋巴管新生相关的核心基因，并预测和分析基于核心基因治疗MI的潜在中药。[方法] 基于GSE66360数据集筛选差异基因，并从GeneCards数据库收集与淋巴管新生相关的基因集，二者取交集构建MI-淋巴管新生DEGs并分析其相关性。在GeneCards数据库收集淋巴管新生相关基因，并对MI数据集GSE66360进行差异化分析，构建MI-淋巴管新生交集基因集并探究其相关性；利用Metascape、GO、KEGG与GSEA等手段对交集基因进行功能与通路分析。基于Lasso回归与SVM-RFE算法筛选特征基因，通过绘制受试者工作特征（ROC）曲线并利用验证集GSE48060对特征基因进行二次验证得到核心基因，并基于核心基因筛选治疗MI的潜在中药。[结果] 本研究在GSE66360中共获得390个差异基因，与淋巴管新生基因取交集，共得到26个MI-淋巴管新生DEGs。富集分析显示交集基因与一氧化氮生物合成、脂多糖反应、白细胞介素-17、核因子 KB、肿瘤坏死因子等功能与信号通路相关。通过Lasso 回归分析、SVM-RFE算法、ROC曲线与验证集二次验证共得到四个核心基因（ADM、IL1RN、IL1B、PFKFB3）。根据4个核心基因筛选出丹参、黄芪等 18味中药，其四气多为寒、温，五味多属苦、甘、辛，归经主要集中于肺、肾、脾经。[结论] ADM、IL1RN、IL1B、PFKFB3可能是基于淋巴管新生治疗MI的潜在基因，并且丹参、黄芪等中药可能为基于此核心基因治疗MI的药物来源。

Abstract:

[Objective] The key differential genes involved in lymphangiogenesis in myocardial infarction(MI) were selected by bioinformatics methods such as Lasso regression and SVM-RFE algorithm,while the potential traditional Chinese medicine(TCM) for the treatment of MI was predicted and analyzed based on the key genes. [Methods] Based on the GSE66360 dataset to screen differential genes and download the set of genes related to lymphangiogenesis from GeneCards database,the two take the intersection to construct the MI-lymphangiogenesis DEGs and analyze the correlation;the intersected genes were enriched for function and pathway by Metascape,GO,KEGG and GSEA. Based on Lasso regression and SVM-RFE algorithm,we screened the featured genes,and utilized GSE48060 for secondary validation of the genes to obtain the core genes,and screened the prevention and treatment of TCM. [Results] A total of 390 differential genes were obtained in GSE66360,and a total of 26 DEGs were obtained by taking the intersection with MI-lymphangiogenesis genes. Enrichment analyses showed that the core genes were related to the functions and signaling pathways of nitric oxide biosynthesis,lipopolysaccharide response,interleukin 17,nuclear factor KB,and tumor necrosis factor,etc. LASSO regression analyses,SVM-RFE algorithms,ROC curves plotting and secondary validation yielded a total of four core genes(ADM,IL1RN,IL1B,PFKFB3). Based on the four core genes,18 TCM such as Danshen and Huangqi were screened,whose four properties were mostly cold and warm,five flavors were mostly bitter,sweet and pungent,and the channel tropism were mainly focused on the lung,kidney and spleen meridians. [Conclusion] ADM,IL1RN,IL1B,and PFKFB3 may be potential genes for the treatment of MI based on lymphangiogenesis,and TCM such as Danshen and Huangqi may be a source of drugs for the treatment of MI based on potential genes.