COVID-19 Mortality Prediction From Deep Learning in a Large Multistate Electronic Health Record and Laboratory Information System Data Set: Algorithm Development and Validation.

BACKGROUND: COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. OBJECTIVE: Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. METHODS: We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient's first positive COVID-19 nucleic acid test result. RESULTS: The GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106). CONCLUSIONS: Our deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19-positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result.

The Unreasonable Effectiveness of Inverse Reinforcement Learning in Advancing Cancer Research.

The "No Free Lunch" theorem states that for any algorithm, elevated performance over one class of problems is offset by its performance over another. Stated differently, no algorithm works for everything. Instead, designing effective algorithms often means exploiting prior knowledge of data relationships specific to a given problem. This "unreasonable efficacy" is especially desirable for complex and seemingly intractable problems in the natural sciences. One such area that is rife with the need for better algorithms is cancer biology-a field where relatively few insights are being generated from relatively large amounts of data. In part, this is due to the inability of mere statistics to reflect cancer as a genetic evolutionary process-one that involves cells actively mutating in order to navigate host barriers, outcompete neighboring cells, and expand spatially. Our work is built upon the central proposition that the Markov Decision Process (MDP) can better represent the process by which cancer arises and progresses. More specifically, by encoding a cancer cell's complex behavior as a MDP, we seek to model the series of genetic changes, or evolutionary trajectory, that leads to cancer as an optimal decision process. We posit that using an Inverse Reinforcement Learning (IRL) approach will enable us to reverse engineer an optimal policy and reward function based on a set of expert demonstrations extracted from the DNA of patient tumors. The inferred reward function and optimal policy can subsequently be used to extrapolate the evolutionary trajectory of any tumor. Here, we introduce a Bayesian nonparametric IRL model (PUR-IRL) where the number of reward functions is a priori unbounded in order to account for uncertainty in cancer data, i.e., the existence of latent trajectories and non-uniform sampling. We show that PUR-IRL is "unreasonably effective" in gaining interpretable and intuitive insights about cancer progression from high-dimensional genome data.