A Kernel to Exploit Informative Missingness in Multivariate Time Series from EHRs

A large fraction of the electronic health records (EHRs) consists of clinical measurements collected over time, such as lab tests and vital signs, which provide important information about a patient's health status. These sequences of clinical measurements are naturally represented as time series, characterized by multiple variables and large amounts of missing data, which complicate the analysis. In this work, we propose a novel kernel which is capable of exploiting both the information from the observed values as well the information hidden in the missing patterns in multivariate time series (MTS) originating e.g. from EHRs. The kernel, called TCK$_{IM}$, is designed using an ensemble learning strategy in which the base models are novel mixed mode Bayesian mixture models which can effectively exploit informative missingness without having to resort to imputation methods. Moreover, the ensemble approach ensures robustness to hyperparameters and therefore TCK$_{IM}$ is particularly well suited if there is a lack of labels - a known challenge in medical applications. Experiments on three real-world clinical datasets demonstrate the effectiveness of the proposed kernel.Comment: 2020 International Workshop on Health Intelligence, AAAI-20. arXiv admin note: text overlap with arXiv:1907.0525

Time series cluster kernels to exploit informative missingness and incomplete label information

The time series cluster kernel (TCK) provides a powerful tool for analysing multivariate time series subject to missing data. TCK is designed using an ensemble learning approach in which Bayesian mixture models form the base models. Because of the Bayesian approach, TCK can naturally deal with missing values without resorting to imputation and the ensemble strategy ensures robustness to hyperparameters, making it particularly well suited for unsupervised learning. However, TCK assumes missing at random and that the underlying missingness mechanism is ignorable, i.e. uninformative, an assumption that does not hold in many real-world applications, such as e.g. medicine. To overcome this limitation, we present a kernel capable of exploiting the potentially rich information in the missing values and patterns, as well as the information from the observed data. In our approach, we create a representation of the missing pattern, which is incorporated into mixed mode mixture models in such a way that the information provided by the missing patterns is effectively exploited. Moreover, we also propose a semi-supervised kernel, capable of taking advantage of incomplete label information to learn more accurate similarities. Experiments on benchmark data, as well as a real-world case study of patients described by longitudinal electronic health record data who potentially suffer from hospital-acquired infections, demonstrate the effectiveness of the proposed method

Machine Learning Methods for Precision Medicine using Patient Electronic Health Records and Mobile Sensor Data

In the field of precision medicine, researchers adopt machine learning techniques to solve health-related problems, while applying such methods needs substantial health data. Electronic health records (EHRs) and mobile sensor data have become two important and abundant sources of health data. However, the modeling techniques for applying such data are still under development. The objective of this dissertation is to develop innovative frameworks of machine learning methods to use EHRs and/or mobile sensor data for disease prediction and precision medicine. The first problem we address is using retrospectively collected EHRs data to learn latent patterns that can inform patient’s health status. To handle data challenges in EHRs, we propose an approach that is based on multivariate generalized linear models in which latent Gaussian processes are introduced to model between-marker correlations over time. Using the inferred latent processes, we integrate irregularly measured health markers of mixed types into composite scores and apply hierarchical clustering to learn latent subgroup structures among patients. We demonstrate the utility of the proposed model through simulation studies and an EHRs dataset for type 2 diabetes (T2D) patients. The next topic we investigate is recommending optimal individualized treatments to patients in EHRs data. To handle the multicategory comparison of treatments and confounding effects among patients, we incorporate the latent subgroups and use the one-versus-one approach to extend a matched learning model. Each matched learning for binary treatments is implemented by a weighted support vector machine with matched pairs of patients. Using the proposed method, we select the optimal treatments from four classes of T2D treatments and achieve a better control of glycated hemoglobin than one-size-fits-all rules for an EHRs dataset. The last problem we explore is using mobile sensor data to predict outcomes and identify objective biomarkers related to adverse posttraumatic neuropsychiatric sequelae. To overcome the difficulties in utilizing mobile sensor data, we develop a two-stage model that considers the measurement resolution and temporal pattern of features collected from mobile sensors. Finally, we apply our method to predict the pain experience of participants who experienced traumatic events, using the data collected from a large-scale cohort study.Doctor of Philosoph

Representation learning for uncertainty-aware clinical decision support

Over the last decade, there has been an increasing trend towards digitalization in healthcare, where a growing amount of patient data is collected and stored electronically. These recorded data are known as electronic health records. They are the basis for state-of-the-art research on clinical decision support so that better patient care can be delivered with the help of advanced analytical techniques like machine learning. Among various technical fields in machine learning, representation learning is about learning good representations from raw data to extract useful information for downstream prediction tasks. Deep learning, a crucial class of methods in representation learning, has achieved great success in many fields such as computer vision and natural language processing. These technical breakthroughs would presumably further advance the research and development of data analytics in healthcare. This thesis addresses clinically relevant research questions by developing algorithms based on state-of-the-art representation learning techniques. When a patient visits the hospital, a physician will suggest a treatment in a deterministic manner. Meanwhile, uncertainty comes into play when the past statistics of treatment decisions from various physicians are analyzed, as they would possibly suggest different treatments, depending on their training and experiences. The uncertainty in clinical decision-making processes is the focus of this thesis. The models developed for supporting these processes will therefore have a probabilistic nature. More specifically, the predictions are predictive distributions in regression tasks and probability distributions over, e.g., different treatment decisions, in classification tasks. The first part of the thesis is concerned with prescriptive analytics to provide treatment recommendations. Apart from patient information and treatment decisions, the outcome after the respective treatment is included in learning treatment suggestions. The problem setting is known as learning individualized treatment rules and is formulated as a contextual bandit problem. A general framework for learning individualized treatment rules using data from observational studies is presented based on state-of-the-art representation learning techniques. From various offline evaluation methods, it is shown that the treatment policy in our proposed framework can demonstrate better performance than both physicians and competitive baselines. Subsequently, the uncertainty-aware regression models in diagnostic and predictive analytics are studied. Uncertainty-aware deep kernel learning models are proposed, which allow the estimation of the predictive uncertainty by a pipeline of neural networks and a sparse Gaussian process. By considering the input data structure, respective models are developed for diagnostic medical image data and sequential electronic health records. Various pre-training methods from representation learning are adapted to investigate their impacts on the proposed models. Through extensive experiments, it is shown that the proposed models delivered better performance than common architectures in most cases. More importantly, uncertainty-awareness of the proposed models is illustrated by systematically expressing higher confidence in more accurate predictions and less confidence in less accurate ones. The last part of the thesis is about missing data imputation in descriptive analytics, which provides essential evidence for subsequent decision-making processes. Rather than traditional mean and median imputation, a more advanced solution based on generative adversarial networks is proposed. The presented method takes the categorical nature of patient features into consideration, which enables the stabilization of the adversarial training. It is shown that the proposed method can better improve the predictive accuracy compared to traditional imputation baselines

Machine Learning Methods To Identify Hidden Phenotypes In The Electronic Health Record

The widespread adoption of Electronic Health Records (EHRs) means an unprecedented amount of patient treatment and outcome data is available to researchers. Research is a tertiary priority in the EHR, where the priorities are patient care and billing. Because of this, the data is not standardized or formatted in a manner easily adapted to machine learning approaches. Data may be missing for a large variety of reasons ranging from individual input styles to differences in clinical decision making, for example, which lab tests to issue. Few patients are annotated at a research quality, limiting sample size and presenting a moving gold standard. Patient progression over time is key to understanding many diseases but many machine learning algorithms require a snapshot, at a single time point, to create a usable vector form. In this dissertation, we develop new machine learning methods and computational workflows to extract hidden phenotypes from the Electronic Health Record (EHR). In Part 1, we use a semi-supervised deep learning approach to compensate for the low number of research quality labels present in the EHR. In Part 2, we examine and provide recommendations for characterizing and managing the large amount of missing data inherent to EHR data. In Part 3, we present an adversarial approach to generate synthetic data that closely resembles the original data while protecting subject privacy. We also introduce a workflow to enable reproducible research even when data cannot be shared. In Part 4, we introduce a novel strategy to first extract sequential data from the EHR and then demonstrate the ability to model these sequences with deep learning

Secondary Analysis of Electronic Health Records

Health Informatics; Ethics; Data Mining and Knowledge Discovery; Statistics for Life Sciences, Medicine, Health Science