通过整合生物信息学和机器学习来开发用于醛固酮瘤的新型诊断模型和潜在药物。

Developing the novel diagnostic model and potential drugs by integrating bioinformatics and machine learning for aldosterone-producing adenomas.

作者信息

Yu Deshui, Zhang Jinxuan, Li Xintao, Xiao Shuwei, Xing Jizhang, Li Jianye

机构信息

Department of Urology, Air Force Medical Center, Beijing, China.

China Medical University, Shenyang, China.

出版信息

Front Mol Biosci. 2024 Jan 4;10:1308754. doi: 10.3389/fmolb.2023.1308754. eCollection 2023.

Abstract

Aldosterone-producing adenomas (APA) are a common cause of primary aldosteronism (PA), a clinical syndrome characterized by hypertension and electrolyte disturbances. If untreated, it may lead to serious cardiovascular complications. Therefore, there is an urgent need for potential biomarkers and targeted drugs for the diagnosis and treatment of aldosteronism. We downloaded two datasets (GSE156931 and GSE60042) from the GEO database and merged them by de-batch effect, then screened the top50 of differential genes using PPI and enriched them, followed by screening the Aldosterone adenoma-related genes (ARGs) in the top50 using three machine learning algorithms. We performed GSEA analysis on the ARGs separately and constructed artificial neural networks based on the ARGs. Finally, the Enrich platform was utilized to identify drugs with potential therapeutic effects on APA by tARGseting the ARGs. We identified 190 differential genes by differential analysis, and then identified the top50 genes by PPI, and the enrichment analysis showed that they were mainly enriched in amino acid metabolic pathways. Then three machine learning algorithms identified five ARGs, namely, SST, RAB3C, PPY, CYP3A4, CDH10, and the ANN constructed on the basis of these five ARGs had better diagnostic effect on APA, in which the AUC of the training set is 1 and the AUC of the validation set is 0.755. And then the Enrich platform identified drugs tARGseting the ARGs with potential therapeutic effects on APA. We identified five ARGs for APA through bioinformatic analysis and constructed Artificial neural network (ANN) based on them with better diagnostic effects, and identified drugs with potential therapeutic effects on APA by tARGseting these ARGs. Our study provides more options for the diagnosis and treatment of APA.

摘要

醛固酮瘤(APA)是原发性醛固酮增多症(PA)的常见病因,PA是一种以高血压和电解质紊乱为特征的临床综合征。若不治疗,可能会导致严重的心血管并发症。因此,迫切需要用于醛固酮增多症诊断和治疗的潜在生物标志物及靶向药物。我们从基因表达综合数据库(GEO数据库)下载了两个数据集(GSE156931和GSE60042),并通过去批次效应将它们合并,然后使用蛋白质-蛋白质相互作用(PPI)筛选出前50个差异基因并进行富集,接着使用三种机器学习算法在这前50个基因中筛选出醛固酮瘤相关基因(ARG)。我们分别对这些ARG进行基因集富集分析(GSEA),并基于这些ARG构建人工神经网络。最后,利用Enrich平台通过靶向这些ARG来识别对APA具有潜在治疗作用的药物。我们通过差异分析鉴定出190个差异基因,然后通过PPI确定前50个基因,富集分析表明它们主要富集在氨基酸代谢途径中。然后三种机器学习算法鉴定出五个ARG,即促生长抑素(SST)、RAB3C、胰多肽(PPY)、细胞色素P450 3A4(CYP3A4)、钙黏蛋白10(CDH10),基于这五个ARG构建的人工神经网络对APA具有较好的诊断效果,其中训练集的曲线下面积(AUC)为1,验证集的AUC为0.755。然后Enrich平台鉴定出靶向这些ARG且对APA具有潜在治疗作用的药物。我们通过生物信息学分析为APA鉴定出五个ARG,并基于它们构建了具有较好诊断效果的人工神经网络,通过靶向这些ARG鉴定出对APA具有潜在治疗作用的药物。我们的研究为APA的诊断和治疗提供了更多选择。

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