RESUMEN
Making health data available for secondary use enables innovative data-driven medical research. Since modern machine learning (ML) methods and precision medicine require extensive amounts of data covering most of the standard and edge cases, it is essential to initially acquire large datasets. This can typically only be achieved by integrating different datasets from various sources and sharing data across sites. To obtain a unified dataset from heterogeneous sources, standard representations and Common Data Models (CDM) are needed. The process of mapping data into these standardized representations is usually very tedious and requires many manual configuration and refinement steps. A potential way to reduce these efforts is to use ML methods not only for data analysis, but also for the integration of health data on the syntactic, structural, and semantic level. However, research on ML-based medical data integration is still in its infancy. In this article, we describe the current state of the literature and present selected methods that appear to have a particularly high potential to improve medical data integration. Moreover, we discuss open issues and possible future research directions.
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Investigación Biomédica , Aprendizaje Automático , SemánticaRESUMEN
Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal and neurological diseases and cancers. Specifically, we trained a neural network to learn disease-specific metabolomic states from 168 circulating metabolic markers measured in 117,981 participants with ~1.4 million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer. For 10-year outcome prediction for 15 endpoints, with and without established metabolic contribution, a combination of age and sex and the metabolomic state equaled or outperformed established predictors. Moreover, metabolomic state added predictive information over comprehensive clinical variables for eight common diseases, including type 2 diabetes, dementia and heart failure. Decision curve analyses showed that predictive improvements translated into clinical utility for a wide range of potential decision thresholds. Taken together, our study demonstrates both the potential and limitations of NMR-derived metabolomic profiles as a multidisease assay to inform on the risk of many common diseases simultaneously.
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Neoplasias de la Mama , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Humanos , Femenino , Metabolómica , Espectroscopía de Resonancia Magnética , Insuficiencia Cardíaca/metabolismoRESUMEN
BACKGROUND: In primary cardiovascular disease prevention, early identification of high-risk individuals is crucial. Genetic information allows for the stratification of genetic predispositions and lifetime risk of cardiovascular disease. However, towards clinical application, the added value over clinical predictors later in life is crucial. Currently, this genotype-phenotype relationship and implications for overall cardiovascular risk are unclear. METHODS: In this study, we developed and validated a neural network-based risk model (NeuralCVD) integrating polygenic and clinical predictors in 395â713 cardiovascular disease-free participants from the UK Biobank cohort. The primary outcome was the first record of a major adverse cardiac event (MACE) within 10 years. We compared the NeuralCVD model with both established clinical scores (SCORE, ASCVD, and QRISK3 recalibrated to the UK Biobank cohort) and a linear Cox-Model, assessing risk discrimination, net reclassification, and calibration over 22 spatially distinct recruitment centres. FINDINGS: The NeuralCVD score was well calibrated and improved on the best clinical baseline, QRISK3 (ΔConcordance index [C-index] 0·01, 95% CI 0·009-0·011; net reclassification improvement (NRI) 0·0488, 95% CI 0·0442-0·0534) and a Cox model (ΔC-index 0·003, 95% CI 0·002-0·004; NRI 0·0469, 95% CI 0·0429-0·0511) in risk discrimination and net reclassification. After adding polygenic scores we found further improvements on population level (ΔC-index 0·006, 95% CI 0·005-0·007; NRI 0·0116, 95% CI 0·0066-0·0159). Additionally, we identified an interaction of genetic information with the pre-existing clinical phenotype, not captured by conventional models. Additional high polygenic risk increased overall risk most in individuals with low to intermediate clinical risk, and age younger than 50 years. INTERPRETATION: Our results demonstrated that the NeuralCVD score can estimate cardiovascular risk trajectories for primary prevention. NeuralCVD learns the transition of predictive information from genotype to phenotype and identifies individuals with high genetic predisposition before developing a severe clinical phenotype. This finding could improve the reprioritisation of otherwise low-risk individuals with a high genetic cardiovascular predisposition for preventive interventions. FUNDING: Charité-Universitätsmedizin Berlin, Einstein Foundation Berlin, and the Medical Informatics Initiative.