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Background: Machine learning (ML) has emerged as a powerful approach for predicting outcomes based on patterns and inferences. Improving prediction of severe coronary artery disease (CAD) has the potential for personalizing prevention and treatment strategies and for identifying individuals that may benefit from cardiac catheterization. We developed a novel ML approach combining traditional cardiac risk factors (CRF) with a single nucleotide polymorphism (SNP) in a gene associated with human CAD ( ID3 rs11574) to enhance prediction of CAD severity; Methods: ML models incorporating CRF along with ID3 genotype at rs11574 were evaluated. The most predictive model, a deep neural network, was used to classify patients into high (&gt;32) and low level (≤32) Gensini severity score. This model was trained on 325 and validated on 82 patients. Prediction performance of the model was summarized by a confusion matrix and area under the receiver operating characteristics curve (ROC-AUC); and Results: Our neural network predicted severity score with 81% and 87% accuracy for the low and the high groups respectively with an ROC-AUC of 0.84 for 82 patients in the test group. The addition of ID3 rs11574 to CRF significantly enhanced prediction accuracy from 65% to 81% in the low group, and 72% to 84% in the high group. Age, high-density lipoprotein (HDL), and systolic blood pressure were the top 3 contributors in predicting severity score; Conclusions: Our neural network including ID3 rs11574 improved prediction of CAD severity over use of Framingham score, which may potentially be helpful for clinical decision making in patients at increased risk of complications from coronary angiography.

A Machine Learning Model Utilizing a Novel SNP Shows Enhanced Prediction of Coronary Artery Disease Severity