A machine learning model utilizing 21 single nucleotide polymorphisms accurately predicted advanced coronary artery calcium, achieving an area under the receiver operating characteristic curve of 0.85 in the replication cohort.
Case-Control (n=348)
Yes
Absolute Event Rate: 0.85% vs 0.61%
p-value: p=<0.001
BACKGROUND: One goal of personalized medicine is leveraging the emerging tools of data science to guide medical decision-making. Achieving this using disparate data sources is most daunting for polygenic traits. To this end, we employed random forests (RFs) and neural networks (NNs) for predictive modeling of coronary artery calcium (CAC), which is an intermediate endo-phenotype of coronary artery disease (CAD). METHODS: CAC score percentile range, and age-matched controls (ClinSeq®; n=16, FHS n=36) with no detectable CAC (all subjects were Caucasian males). These inputs included clinical variables and genotypes of 56 single nucleotide polymorphisms (SNPs) ranked highest in terms of their nominal correlation with the advanced CAC state in the discovery cohort. Predictive performance was assessed by computing the areas under receiver operating characteristic curves (ROC-AUC). RESULTS: RF models trained and tested with clinical variables generated ROC-AUC values of 0.69 and 0.61 in the discovery and replication cohorts, respectively. In contrast, in both cohorts, the set of SNPs derived from the discovery cohort were highly predictive (ROC-AUC ≥0.85) with no significant change in predictive performance upon integration of clinical and genotype variables. Using the 21 SNPs that produced optimal predictive performance in both cohorts, we developed NN models trained with ClinSeq®; data and tested with FHS data and obtained high predictive accuracy (ROC-AUC=0.80-0.85) with several topologies. Several CAD and "vascular aging" related biological processes were enriched in the network of genes constructed from the predictive SNPs. CONCLUSIONS: We identified a molecular network predictive of advanced coronary calcium using genotype data from ClinSeq®; and FHS cohorts. Our results illustrate that machine learning tools, which utilize complex interactions between disease predictors intrinsic to the pathogenesis of polygenic disorders, hold promise for deriving predictive disease models and networks.
Oguz et al. (Thu,) conducted a case-control in Advanced coronary artery calcium (n=348). 21-SNP machine learning predictive model vs. Clinical variables predictive model was evaluated on Area under the receiver operating characteristic curve (ROC-AUC) in the replication cohort (p=<0.001). A machine learning model utilizing 21 single nucleotide polymorphisms accurately predicted advanced coronary artery calcium, achieving an area under the receiver operating characteristic curve of 0.85 in the replication cohort.