Joint Associations of Multiple Dietary Components With Cardiovascular Disease Risk: A Machine-Learning Approach.
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ABSTRACT:
SUBMITTER: Zhao Y
PROVIDER: S-EPMC8245893 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDietary restriction (DR) is the most studied pro-longevity intervention; however, a complete understanding of its underlying mechanisms remains elusive, and new research directions may emerge from the identification of novel DR-related genes and DR-related genetic features.ResultsThis work used a Machine Learning (ML) approach to classify ageing-related genes as DR-related or NotDR-related using 9 different types of predictive features: PathDIP pathways, two types of features based on KEGG pathways, two types of Protein-Protein Interactions (PPI) features, Gene Ontology (GO) terms, Genotype Tissue Expression (GTEx) expression features, GeneFriends co-expression features and protein sequence descriptors. Our findings suggested that features biased towards curated knowledge (i.e. GO terms and biological pathways), had the greatest predictive power, while unbiased features (mainly gene expression and co-expression data) have the least predictive power. Moreover, a combination of all the feature types diminished the predictive power compared to predictions based on curated knowledge. Feature importance analysis on the two most predictive classifiers mostly corroborated existing knowledge and supported recent findings linking DR to the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) signalling pathway and G protein-coupled receptors (GPCR). We then used the two strongest combinations of feature type and ML algorithm to predict DR-relatedness among ageing-related genes currently lacking DR-related annotations in the data, resulting in a set of promising candidate DR-related genes (GOT2, GOT1, TSC1, CTH, GCLM, IRS2 and SESN2) whose predicted DR-relatedness remain to be validated in future wet-lab experiments.ConclusionsThis work demonstrated the strong potential of ML-based techniques to identify DR-associated features as our findings are consistent with literature and recent discoveries. Although the inference of new DR-related mechanistic findings based solely on GO terms and biological pathways was limited due to their knowledge-driven nature, the predictive power of these two features types remained useful as it allowed inferring new promising candidate DR-related genes.
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Project description:BackgroundPatients with atrial fibrillation (AF) usually have a heterogeneous co-morbid history, with dynamic changes in risk factors impacting on multiple adverse outcomes. We investigated a large prospective cohort of patients with multimorbidity, using a machine-learning approach, accounting for the dynamic nature of comorbidity risks and incident AF.MethodsUsing machine-learning, we studied a prospective US cohort using medical/pharmacy databases of 1 091 911 patients, with an incident AF cohort of 14 078 and non-AF cohort of 1 077 833 enrolled in the 4-year study. Five incident clinical outcomes (heart failure, stroke, myocardial infarction, major bleeding, and cognitive impairment) were examined in relationship to AF status (AF vs non-AF), diverse multi-morbid (conditions and medications) history, and demographic parameters (age and gender), with supervised machine-learning techniques.ResultsComplex inter-relationships of various comorbidities were uncovered for AF cases, leading to 6-fold higher risk of heart failure relative to the non-AF cohort (OR 6.02, 95% CI 5.72-6.33), followed by myocardial infarction (OR=2.68), stroke (OR=2.19), and major bleeding (OR=1.36). Supervised machine learning algorithms on the original populations yielded comparable results for both neural network and logistic regression algorithms in terms of discriminant validity, with c-indexes for incident adverse outcomes: heart failure (0.924, 95%CI 0.923-0.925), stroke (0.871, 95%CI 0.869-0.873), myocardial infarction (0.901, 95% CI 0.899-0.903), major bleeding (0.700, 95%CI 0.697-0.703), and cognitive impairment (0.919, 95% CI 0.9170.921). External calibration of all models demonstrated a good fit between the predicted probabilities and observed events. Decision curve analysis demonstrated that the obtained models were much more clinically useful than the "treat all" strategy.ConclusionsComplex multimorbidity relationships uncovered using a machine learning approach for incident AF cases have major consequences for integrated care management, with implications for risk stratification and adverse clinical outcomes. This approach may facilitate automated approaches in the presence of multimorbidity, potentially helping decision making.
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Project description:IntroductionThis study developed a novel risk assessment model to predict the occurrence of cardiovascular disease (CVD) events. It uses a Genetic Algorithm (GA) to develop an easy-to-use model with high accuracy, calibrated based on the Isfahan Cohort Study (ICS) database.MethodsThe ICS was a population-based prospective cohort study of 6,504 healthy Iranian adults aged ≥ 35 years followed for incident CVD over ten years, from 2001 to 2010. To develop a risk score, the problem of predicting CVD was solved using a well-designed GA, and finally, the results were compared with classic machine learning (ML) and statistical methods.ResultsA number of risk scores such as the WHO, and PARS models were utilized as the baseline for comparison due to their similar chart-based models. The Framingham and PROCAM models were also applied to the dataset, with the area under a Receiver Operating Characteristic curve (AUROC) equal to 0.633 and 0.683, respectively. However, the more complex Deep Learning model using a three-layered Convolutional Neural Network (CNN) performed best among the ML models, with an AUROC of 0.74, and the GA-based eXplanaible Persian Atherosclerotic CVD Risk Stratification (XPARS) showed higher performance compared to the statistical methods. XPARS with eight features showed an AUROC of 0.76, and the XPARS with four features, showed an AUROC of 0.72.ConclusionA risk model that is extracted using GA substantially improves the prediction of CVD compared to conventional methods. It is clear, interpretable and can be a suitable replacement for conventional statistical methods.
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Project description:BackgroundCurrent approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction.MethodsProspective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the 'receiver operating curve' (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins).Findings24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723-0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739-0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755-0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755-0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759-0.769). The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm.ConclusionsMachine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others.
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