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Published on: September 20, 2024
Machine learning integrated clinical-proteomics data identifies a 6-protein panel signature for atherosclerotic
Mª Jesús Extremera-García1,2, Marta Rojas-Torres1, Blanca Priego-Torres3
1Biomedicine, Biotechnology and Public Health Department, Cádiz University, Cádiz, Spain//Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain.
Insights
Machine learning identified a 6-protein panel to detect atherosclerosis. This panel accurately identifies patients at risk for cardiovascular events, improving early diagnosis and personalized treatment strategies.
Area of Science:
- Cardiovascular Research
- Biomarker Discovery
- Machine Learning in Medicine
Background:
- Atherosclerosis is a leading cause of global mortality, driven by lipid accumulation and arterial wall inflammation.
- Early identification of at-risk patients is critical for preventing thrombotic events and enabling personalized treatments.
Purpose of the Study:
- To leverage machine learning (ML) for enhanced diagnostics and biomarker discovery in atherosclerosis.
- To identify a robust protein signature for discriminating atherosclerosis severity using clinical and proteomic data.
Main Methods:
- Applied five ML classification algorithms to clinical and serum proteomic data from patients with carotid atherosclerotic stenosis (AT), dyslipidemic patients (DLP), and healthy controls (HC).
- Integrated clinical and proteomic data for improved patient stratification compared to individual analyses.
- Validated the identified protein panel in an independent cohort of patients with acute atherothrombotic stroke.
Main Results:
- Identified a 6-protein panel (B2M, GPV, MMP9, PLF4, TSP1, and FB isoforms) with high diagnostic accuracy (ROC-AUC > 0.9) for discriminating AT patients.
- The combined clinical-proteomic ML approach demonstrated superior patient stratification capabilities.
- Validated the panel's potential as a biomarker for atherosclerosis severity in an external cohort.
Conclusions:
- The 6-protein panel serves as a promising biomarker for assessing atherosclerosis severity and identifying at-risk individuals.
- The identified biomarkers implicate platelet activation, angiogenesis, and intraplaque hemorrhage in atherosclerosis.
- Highlights the need for multipathway therapeutic strategies to prevent adverse thrombotic events in atherosclerosis.
Abstract:
Atherosclerosis, a major cause of adverse cardiovascular events and mortality rates worldwide, stems from sustained lipid accumulation and subsequent chronic inflammation within the arterial walls. An early identification of patients at risk is crucial to prevent life-threatening thrombotic events and provide effective and personalized treatments. Leveraging the power of machine learning (ML) to enhance diagnostics and biomarker discovery, we applied a high-throughput approach using five ML classification algorithms (MLCA), integrating clinical and serum proteomic data from patients with carotid atherosclerotic stenosis (AT, n:60), dyslipidemic patients (DLP, n:55), and healthy controls (HC, n:66). As a result, a robust 6-protein panel (B2M, GPV, MMP9, PLF4, TSP1, and FB isoforms) was identified with a ROC-AUC value > 0.9 for all algorithms applied, highly discriminating AT patients compared to DLP or CTRL. The levels of these proteins were further validated in an independent external cohort, including patients presenting with acute atherothrombotic stroke, corroborating the potential of this panel as biomarker for atherosclerosis severity. In addition, the combined clinical-proteomic ML approach provided a more accurate patient stratification than the clinical or proteomic analysis alone. Mechanistically, the identified biomarkers highlight the importance of platelet activation, uncontrolled angiogenesis and intraplaque haemorrhage in the atherosclerotic process, underscoring the need for multipathway therapies to prevent unwanted thrombotic events.
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