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解锁 microRNAs 的潜力:机器学习为心肌梗死诊断识别关键生物标志物。

Unlocking the potential of microRNAs: machine learning identifies key biomarkers for myocardial infarction diagnosis.

机构信息

Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Cardiovasc Diabetol. 2023 Sep 11;22(1):247. doi: 10.1186/s12933-023-01957-7.

Abstract

BACKGROUND

MicroRNAs (miRNAs) play a crucial role in regulating adaptive and maladaptive responses in cardiovascular diseases, making them attractive targets for potential biomarkers. However, their potential as novel biomarkers for diagnosing cardiovascular diseases requires systematic evaluation.

METHODS

In this study, we aimed to identify a key set of miRNA biomarkers using integrated bioinformatics and machine learning analysis. We combined and analyzed three gene expression datasets from the Gene Expression Omnibus (GEO) database, which contains peripheral blood mononuclear cell (PBMC) samples from individuals with myocardial infarction (MI), stable coronary artery disease (CAD), and healthy individuals. Additionally, we selected a set of miRNAs based on their area under the receiver operating characteristic curve (AUC-ROC) for separating the CAD and MI samples. We designed a two-layer architecture for sample classification, in which the first layer isolates healthy samples from unhealthy samples, and the second layer classifies stable CAD and MI samples. We trained different machine learning models using both biomarker sets and evaluated their performance on a test set.

RESULTS

We identified hsa-miR-21-3p, hsa-miR-186-5p, and hsa-miR-32-3p as the differentially expressed miRNAs, and a set including hsa-miR-186-5p, hsa-miR-21-3p, hsa-miR-197-5p, hsa-miR-29a-5p, and hsa-miR-296-5p as the optimum set of miRNAs selected by their AUC-ROC. Both biomarker sets could distinguish healthy from not-healthy samples with complete accuracy. The best performance for the classification of CAD and MI was achieved with an SVM model trained using the biomarker set selected by AUC-ROC, with an AUC-ROC of 0.96 and an accuracy of 0.94 on the test data.

CONCLUSIONS

Our study demonstrated that miRNA signatures derived from PBMCs could serve as valuable novel biomarkers for cardiovascular diseases.

摘要

背景

MicroRNAs(miRNAs)在调节心血管疾病的适应性和失调性反应中发挥着关键作用,使其成为有潜力的生物标志物。然而,它们作为诊断心血管疾病的新型生物标志物的潜力需要系统的评估。

方法

在这项研究中,我们旨在使用综合的生物信息学和机器学习分析来确定一组关键的 miRNA 生物标志物。我们结合并分析了三个来自基因表达综合数据库(GEO)的基因表达数据集,这些数据集包含了心肌梗死(MI)、稳定型冠状动脉疾病(CAD)和健康个体的外周血单核细胞(PBMC)样本。此外,我们基于其用于区分 CAD 和 MI 样本的受试者工作特征曲线(ROC)下面积(AUC-ROC)选择了一组 miRNA。我们设计了一个两层架构用于样本分类,其中第一层将健康样本与不健康样本分开,第二层则对稳定型 CAD 和 MI 样本进行分类。我们使用两种生物标志物集训练了不同的机器学习模型,并在测试集上评估了它们的性能。

结果

我们确定 hsa-miR-21-3p、hsa-miR-186-5p 和 hsa-miR-32-3p 为差异表达的 miRNAs,而一组包括 hsa-miR-186-5p、hsa-miR-21-3p、hsa-miR-197-5p、hsa-miR-29a-5p 和 hsa-miR-296-5p 的 miRNA 则是根据其 AUC-ROC 选择的最佳 miRNA 集。两种生物标志物集都可以准确地将健康样本与不健康样本区分开来。使用 AUC-ROC 选择的生物标志物集训练的 SVM 模型在 CAD 和 MI 的分类中表现最佳,在测试数据上的 AUC-ROC 为 0.96,准确性为 0.94。

结论

我们的研究表明,源自 PBMC 的 miRNA 特征可以作为心血管疾病有价值的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/446b/10496209/df4cff0e1166/12933_2023_1957_Fig1_HTML.jpg

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