Collaborating Authors

Patient Similarity Analysis with Longitudinal Health Data Machine Learning

Healthcare professionals have long envisioned using the enormous processing powers of computers to discover new facts and medical knowledge locked inside electronic health records. These vast medical archives contain time-resolved information about medical visits, tests and procedures, as well as outcomes, which together form individual patient journeys. By assessing the similarities among these journeys, it is possible to uncover clusters of common disease trajectories with shared health outcomes. The assignment of patient journeys to specific clusters may in turn serve as the basis for personalized outcome prediction and treatment selection. This procedure is a non-trivial computational problem, as it requires the comparison of patient data with multi-dimensional and multi-modal features that are captured at different times and resolutions. In this review, we provide a comprehensive overview of the tools and methods that are used in patient similarity analysis with longitudinal data and discuss its potential for improving clinical decision making.

Patient Subtyping with Disease Progression and Irregular Observation Trajectories Machine Learning

Patient subtyping based on temporal observations can lead to significantly nuanced subtyping that acknowledges the dynamic characteristics of diseases. Existing methods for subtyping trajectories treat the evolution of clinical observations as a homogeneous process or employ data available at regular intervals. In reality, diseases may have transient underlying states and a state-dependent observation pattern. In our paper, we present an approach to subtype irregular patient data while acknowledging the underlying progression of disease states. Our approach consists of two components: a probabilistic model to determine the likelihood of a patient's observation trajectory and a mixture model to measure similarity between asynchronous patient trajectories. We demonstrate our model by discovering subtypes of progression to hemodynamic instability (requiring cardiovascular intervention) in a patient cohort from a multi-institution ICU dataset. We find three primary patterns: two of which show classic signs of decompensation (rising heart rate with dropping blood pressure), with one of these showing a faster course of decompensation than the other. The third pattern has transient period of low heart rate and blood pressure. We also show that our model results in a 13% reduction in average cross-entropy error compared to a model with no state progression when forecasting vital signs.

Forecasting Individualized Disease Trajectories using Interpretable Deep Learning Machine Learning

Disease progression models are instrumental in predicting individual-level health trajectories and understanding disease dynamics. Existing models are capable of providing either accurate predictions of patients' prognoses or clinically interpretable representations of disease pathophysiology, but not both. In this paper, we develop the phased attentive state space (PASS) model of disease progression, a deep probabilistic model that captures complex representations for disease progression while maintaining clinical interpretability. Unlike Markovian state space models which assume memoryless dynamics, PASS uses an attention mechanism to induce "memoryful" state transitions, whereby repeatedly updated attention weights are used to focus on past state realizations that best predict future states. This gives rise to complex, non-stationary state dynamics that remain interpretable through the generated attention weights, which designate the relationships between the realized state variables for individual patients. PASS uses phased LSTM units (with time gates controlled by parametrized oscillations) to generate the attention weights in continuous time, which enables handling irregularly-sampled and potentially missing medical observations. Experiments on data from a real-world cohort of patients show that PASS successfully balances the tradeoff between accuracy and interpretability: it demonstrates superior predictive accuracy and learns insightful individual-level representations of disease progression.

Clustering Longitudinal Clinical Marker Trajectories from Electronic Health Data: Applications to Phenotyping and Endotype Discovery

AAAI Conferences

Diseases such as autism, cardiovascular disease, and the autoimmune disorders are difficult to treat because of the remarkable degree of variation among affected individuals. Subtyping research seeks to refine the definition of such complex, multi-organ diseases by identifying homogeneous patient subgroups. In this paper, we propose the Probabilistic Subtyping Model (PSM) to identify subgroups based on clustering individual clinical severity markers. This task is challenging due to the presence of nuisance variability — variations in measurements that are not due to disease subtype — which, if not accounted for, generate biased estimates for the group-level trajectories. Measurement sparsity and irregular sampling patterns pose additional challenges in clustering such data. PSM uses a hierarchical model to account for these different sources of variability. Our experiments demonstrate that by accounting for nuisance variability, PSM is able to more accurately model the marker data. We also discuss novel subtypes discovered using PSM and the resulting clinical hypotheses that are now the subject of follow up clinical experiments.

Scalable Modeling of Multivariate Longitudinal Data for Prediction of Chronic Kidney Disease Progression Machine Learning

Prediction of the future trajectory of a disease is an important challenge for personalized medicine and population health management. However, many complex chronic diseases exhibit large degrees of heterogeneity, and furthermore there is not always a single readily available biomarker to quantify disease severity. Even when such a clinical variable exists, there are often additional related biomarkers routinely measured for patients that may better inform the predictions of their future disease state. To this end, we propose a novel probabilistic generative model for multivariate longitudinal data that captures dependencies between multivariate trajectories. We use a Gaussian process based regression model for each individual trajectory, and build off ideas from latent class models to induce dependence between their mean functions. We fit our method using a scalable variational inference algorithm to a large dataset of longitudinal electronic patient health records, and find that it improves dynamic predictions compared to a recent state of the art method. Our local accountable care organization then uses the model predictions during chart reviews of high risk patients with chronic kidney disease.