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Published on: September 20, 2024
Prediction Power on Cardiovascular Disease of Neuroimmune Guidance Cues Expression by Peripheral Blood Monocytes
Huayu Zhang1, Edwin O W Bredewold1, Dianne Vreeken1
1Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine, Leiden University Medical Center, Albinusdreef, 22333 ZA Leiden, The Netherlands.
Insights
Circulating monocyte gene expression of neuroimmune guidance cues, including SEMA6B, SEMA6D, and EPHA2, can predict cardiovascular disease outcomes. This finding offers new insights into atherosclerosis development and potential diagnostic markers.
Area of Science:
- Cardiovascular Research
- Immunology
- Genomics
Background:
- Atherosclerosis, a primary cause of cardiovascular disease mortality, involves monocyte infiltration into artery walls.
- Understanding monocyte functional changes through gene expression is crucial for predicting disease outcomes.
- Neuroimmune guidance cues are signaling proteins increasingly recognized for their role in monocyte function.
Purpose of the Study:
- To investigate the predictive value of neuroimmune guidance cue expression in circulating monocytes for cardiovascular disease (CVD).
- To classify CVD patients and healthy individuals based on monocyte gene expression profiles.
- To identify specific neuroimmune guidance cues associated with CVD outcomes.
Main Methods:
- Utilized the CIRCULATING CELLS study cohort.
- Employed high-throughput transcriptome profiling and cytometric methods for circulating cells.
- Assessed various machine-learning methods, including linear discriminant analysis, Naïve Bayesian, and stochastic gradient boost models.
Main Results:
- Machine learning models achieved perfect or near-perfect sensitivity and specificity in classifying CVD patients.
- Expression levels of SEMA6B, SEMA6D, and EPHA2 in circulating monocytes were identified as significant predictors of CVD outcome.
- Demonstrated the utility of analyzing gene expression patterns in monocytes for CVD risk stratification.
Conclusions:
- Circulating monocyte expression of specific neuroimmune guidance cues (SEMA6B, SEMA6D, EPHA2) holds predictive value for cardiovascular disease.
- Machine learning effectively analyzes complex human datasets to identify disease biomarkers.
- This research provides a foundation for developing novel diagnostic strategies for atherosclerosis and cardiovascular disease.
Abstract:
Atherosclerosis is the underlying pathology in a major part of cardiovascular disease, the leading cause of mortality in developed countries. The infiltration of monocytes into the vessel walls of large arteries is a key denominator of atherogenesis, making monocytes accountable for the development of atherosclerosis. With the development of high-throughput transcriptome profiling platforms and cytometric methods for circulating cells, it is now feasible to study in-depth the predicted functional change of circulating monocytes reflected by changes of gene expression in certain pathways and correlate the changes to disease outcome. Neuroimmune guidance cues comprise a group of circulating- and cell membrane-associated signaling proteins that are progressively involved in monocyte functions. Here, we employed the CIRCULATING CELLS study cohort to classify cardiovascular disease patients and healthy individuals in relation to their expression of neuroimmune guidance cues in circulating monocytes. To cope with the complexity of human datasets featured by noisy data, nonlinearity and multidimensionality, we assessed various machine-learning methods. Of these, the linear discriminant analysis, Naïve Bayesian model and stochastic gradient boost model yielded perfect or near-perfect sensibility and specificity and revealed that expression levels of the neuroimmune guidance cues SEMA6B, SEMA6D and EPHA2 in circulating monocytes were of predictive values for cardiovascular disease outcome.
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