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Register a new userLearning Multimorbidity Patterns from Electronic Health Records Using Non-negative Matrix Factorisation
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Multimorbidity, or the presence of several medical conditions in the same individual, has been increasing in the population, both in absolute and relative terms. However, multimorbidity remains poorly understood, and the evidence from existing research to describe its burden, determinants and consequences has been limited. Previous studies attempting to understand multimorbidity patterns are often cross-sectional and do not explicitly account for multimorbidity patterns evolution over time; some of them are based on small datasets and/or use arbitrary and narrow age ranges; and those that employed advanced models, usually lack appropriate benchmarking and validations. In this study, we (1) introduce a novel approach for using Non-negative Matrix Factorisation (NMF) for temporal phenotyping (i.e., simultaneously mining disease clusters and their trajectories); (2) provide quantitative metrics for the evaluation of disease clusters from such studies; and (3) demonstrate how the temporal characteristics of the disease clusters that result from our model can help mine multimorbidity networks and generate new hypotheses for the emergence of various multimorbidity patterns over time. We trained and evaluated our models on one of the worlds largest electronic health records (EHR), with 7 million patients, from which over 2 million where relevant to this study.
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Electronic phenotyping is the task of ascertaining whether an individual has a medical condition of interest by analyzing their medical record and is foundational in clinical informatics. Increasingly, electronic phenotyping is performed via supervised learning. We investigate the effectiveness of multitask learning for phenotyping using electronic health records (EHR) data. Multitask learning aims to improve model performance on a target task by jointly learning additional auxiliary tasks and has been used in disparate areas of machine learning. However, its utility when applied to EHR data has not been established, and prior work suggests that its benefits are inconsistent. We present experiments that elucidate when multitask learning with neural nets improves performance for phenotyping using EHR data relative to neural nets trained for a single phenotype and to well-tuned logistic regression baselines. We find that multitask neural nets consistently outperform single-task neural nets for rare phenotypes but underperform for relatively more common phenotypes. The effect size increases as more auxiliary tasks are added. Moreover, multitask learning reduces the sensitivity of neural nets to hyperparameter settings for rare phenotypes. Last, we quantify phenotype complexity and find that neural nets trained with or without multitask learning do not improve on simple baselines unless the phenotypes are sufficiently complex.
Analyzing electronic health records (EHR) poses significant challenges because often few samples are available describing a patients health and, when available, their information content is highly diverse. The problem we consider is how to integrate sparsely sampled longitudinal data, missing measurements informative of the underlying health status and fixed demographic information to produce estimated survival distributions updated through a patients follow up. We propose a nonparametric probabilistic model that generates survival trajectories from an ensemble of Bayesian trees that learns variable interactions over time without specifying beforehand the longitudinal process. We show performance improvements on Primary Biliary Cirrhosis patient data.
We present a fast variational Bayesian algorithm for performing non-negative matrix factorisation and tri-factorisation. We show that our approach achieves faster convergence per iteration and timestep (wall-clock) than Gibbs sampling and non-probabilistic approaches, and do not require additional samples to estimate the posterior. We show that in particular for matrix tri-factorisation convergence is difficult, but our variational Bayesian approach offers a fast solution, allowing the tri-factorisation approach to be used more effectively.
Predictive modeling with electronic health record (EHR) data is anticipated to drive personalized medicine and improve healthcare quality. Constructing predictive statistical models typically requires extraction of curated predictor variables from normalized EHR data, a labor-intensive process that discards the vast majority of information in each patients record. We propose a representation of patients entire, raw EHR records based on the Fast Healthcare Interoperability Resources (FHIR) format. We demonstrate that deep learning methods using this representation are capable of accurately predicting multiple medical events from multiple centers without site-specific data harmonization. We validated our approach using de-identified EHR data from two U.S. academic medical centers with 216,221 adult patients hospitalized for at least 24 hours. In the sequential format we propose, this volume of EHR data unrolled into a total of 46,864,534,945 data points, including clinical notes. Deep learning models achieved high accuracy for tasks such as predicting in-hospital mortality (AUROC across sites 0.93-0.94), 30-day unplanned readmission (AUROC 0.75-0.76), prolonged length of stay (AUROC 0.85-0.86), and all of a patients final discharge diagnoses (frequency-weighted AUROC 0.90). These models outperformed state-of-the-art traditional predictive models in all cases. We also present a case-study of a neural-network attribution system, which illustrates how clinicians can gain some transparency into the predictions. We believe that this approach can be used to create accurate and scalable predictions for a variety of clinical scenarios, complete with explanations that directly highlight evidence in the patients chart.
Non-negative Matrix Factorisation (NMF) has been extensively used in machine learning and data analytics applications. Most existing variations of NMF only consider how each row/column vector of factorised matrices should be shaped, and ignore the relationship among pairwise rows or columns. In many cases, such pairwise relationship enables better factorisation, for example, image clustering and recommender systems. In this paper, we propose an algorithm named, Relative Pairwise Relationship constrained Non-negative Matrix Factorisation (RPR-NMF), which places constraints over relative pairwise distances amongst features by imposing penalties in a triplet form. Two distance measures, squared Euclidean distance and Symmetric divergence, are used, and exponential and hinge loss penalties are adopted for the two measures respectively. It is well known that the so-called multiplicative update rules result in a much faster convergence than gradient descend for matrix factorisation. However, applying such update rules to RPR-NMF and also proving its convergence is not straightforward. Thus, we use reasonable approximations to relax the complexity brought by the penalties, which are practically verified. Experiments on both synthetic datasets and real datasets demonstrate that our algorithms have advantages on gaining close approximation, satisfying a high proportion of expected constraints, and achieving superior performance compared with other algorithms.
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