Predicting individual and population risk for disease outcomes and identifying persons at elevated risk is a key prerequisite for targeting interventions to improve health. However, current risk stratification tools for the common, chronic diseases that develop over the lifecourse and represent the majority of disease morbidity, mortality and healthcare costs are aging and achieve only moderate predictive performance. In some common, highly morbid conditions such as mental illness no risk stratification tools are yet available. There is an urgent need to improve predictive performance for chronic diseases and understand how cumulative, multifactorial risks aggregate over time so that intervention programs can be targeted earlier and more effectively in the disease course. Chronic diseases are the end outcomes of multifactorial risks that increment over years and represent cumulative, temporally-sensitive risk pathways. However, tools in current clinical use were constructed in older data and utilize inputs from a single data collection step. Here, we present RiskPath, a multistep deep learning method for temporally-sensitive biomedical risk prediction tailored for the constraints and demands of biomedical practice that achieves very strong performance and full translational explainability. RiskPath delineates and quantifies cumulative multifactorial risk pathways and allows the user to explore performance-complexity tradeoffs and constrain models as required by clinical use cases. Our results highlight the potential for developing a new generation of risk stratification tools and risk pathway mapping in time-dependent diseases and health outcomes by leveraging powerful timeseries deep learning methods in the wealth of biomedical data now appearing in large, longitudinal open science datasets.

The authors have declared no competing interest.

This work was supported by the National Institute of Mental Health under award R00MH118359

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The IRB of the University of Utah waived ethical approval of this work and deemed it Not Human Subjects research.

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