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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Machine learning-based mRNA signature in early acute myocardial infarction patients: the perspective toward
Hai-Hua Pan1, Na Yuan1, Ling-Yan He2
1The First Hospital of Jiaxing Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314001, People's Republic of China.
Insights
This study identifies novel biomarkers like CLEC2D, TCN2, and CCR1 for early acute myocardial infarction (AMI) risk in coronary artery disease (CAD) patients. A machine learning model accurately predicts AMI, aiding early diagnosis.
Area of Science:
- Immunology
- Bioinformatics
- Cardiovascular Research
Background:
- Patients with stable coronary artery disease (CAD) face ongoing risks of acute myocardial infarction (AMI).
- Early detection and prediction of AMI are crucial for patient outcomes.
- Understanding the immunological underpinnings of AMI is essential for personalized medicine.
Purpose of the Study:
- To identify pivotal biomarkers and dynamic immune cell changes associated with early acute myocardial infarction (AMI).
- To develop a machine learning-based diagnostic model for predicting AMI occurrence.
- To explore the role of monocytes and cell-cell communication in AMI pathogenesis.
Main Methods:
- Analysis of peripheral blood mRNA data using machine learning and bioinformatics strategies.
- Deconvolution of immune cell subtypes with CIBERSORT and weighted gene co-expression network analysis (WGCNA).
- Unsupervised clustering for AMI patient stratification and development of a predictive diagnostic model.
Main Results:
- Identification of potential early AMI biomarkers: CLEC2D, TCN2, and CCR1.
- Monocytes identified as a key immune cell population involved in AMI.
- Elevated CCR1 and TCN2 expression in early AMI compared to stable CAD.
- A glmBoost+Enet [alpha=0.9] machine learning model demonstrated high predictive accuracy.
Conclusions:
- The study provides insights into biomarkers and immune cells critical for early AMI pathogenesis.
- Identified biomarkers and the diagnostic model offer potential for auxiliary diagnostic and predictive applications in AMI.
- This research supports a personalized and predictive approach to managing CAD patients at risk of AMI.
Abstract:
Patients diagnosed with stable coronary artery disease (CAD) are at continued risk of experiencing acute myocardial infarction (AMI). This study aims to unravel the pivotal biomarkers and dynamic immune cell changes, from an immunological, predictive, and personalized viewpoint, by implementing a machine-learning approach and a composite bioinformatics strategy. Peripheral blood mRNA data from different datasets were analyzed, and CIBERSORT was used for deconvoluting human immune cell subtype expression matrices. Weighted gene co-expression network analysis (WGCNA) in single-cell and bulk transcriptome levels was conducted to explore possible biomarkers for AMI, with a particular emphasis on examining monocytes and their involvement in cell-cell communication. Unsupervised cluster analysis was performed to categorize AMI patients into different subtypes, and machine learning methods were employed to construct a comprehensive diagnostic model to predict the occurrence of early AMI. Finally, RT-qPCR on peripheral blood samples collected from patients validated the clinical utility of the machine learning-based mRNA signature and hub biomarkers. The study identified potential biomarkers for early AMI, including CLEC2D, TCN2, and CCR1, and found that monocytes may play a vital role in AMI samples. Differential analysis revealed that CCR1 and TCN2 exhibited elevated expression levels in early AMI compared to stable CAD. Machine learning methods showed that the glmBoost+Enet [alpha=0.9] model achieved high predictive accuracy in the training set, external validation sets, and clinical samples in our hospital. The study provided comprehensive insights into potential biomarkers and immune cell populations involved in the pathogenesis of early AMI. The identified biomarkers and the constructed comprehensive diagnostic model hold great promise for predicting the occurrence of early AMI and can serve as auxiliary diagnostic or predictive biomarkers.
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