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Register a new userDisease Progression Modeling Workbench 360
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Added by
Parthasarathy Suryanarayanan
Publication date
2021
fields
Informatics Engineering
and research's language is
English
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In this work we introduce Disease Progression Modeling workbench 360 (DPM360) opensource clinical informatics framework for collaborative research and delivery of healthcare AI. DPM360, when fully developed, will manage the entire modeling life cycle, from data analysis (e.g., cohort identification) to machine learning algorithm development and prototyping. DPM360 augments the advantages of data model standardization and tooling (OMOP-CDM, Athena, ATLAS) provided by the widely-adopted OHDSI initiative with a powerful machine learning training framework, and a mechanism for rapid prototyping through automatic deployment of models as containerized services to a cloud environment.
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Analyzing disease progression patterns can provide useful insights into the disease processes of many chronic conditions. These analyses may help inform recruitment for prevention trials or the development and personalization of treatments for those affected. We learn disease progression patterns using Hidden Markov Models (HMM) and distill them into distinct trajectories using visualization methods. We apply it to the domain of Type 1 Diabetes (T1D) using large longitudinal observational data from the T1DI study group. Our method discovers distinct disease progression trajectories that corroborate with recently published findings. In this paper, we describe the iterative process of developing the model. These methods may also be applied to other chronic conditions that evolve over time.
Ability to quantify and predict progression of a disease is fundamental for selecting an appropriate treatment. Many clinical metrics cannot be acquired frequently either because of their cost (e.g. MRI, gait analysis) or because they are inconvenient or harmful to a patient (e.g. biopsy, x-ray). In such scenarios, in order to estimate individual trajectories of disease progression, it is advantageous to leverage similarities between patients, i.e. the covariance of trajectories, and find a latent representation of progression. Most of existing methods for estimating trajectories do not account for events in-between observations, what dramatically decreases their adequacy for clinical practice. In this study, we develop a machine learning framework named Coordinatewise-Soft-Impute (CSI) for analyzing disease progression from sparse observations in the presence of confounding events. CSI is guaranteed to converge to the global minimum of the corresponding optimization problem. Experimental results also demonstrates the effectiveness of CSI using both simulated and real dataset.
We model Alzheimers disease (AD) progression by combining differential equations (DEs) and reinforcement learning (RL) with domain knowledge. DEs provide relationships between some, but not all, factors relevant to AD. We assume that the missing relationships must satisfy general criteria about the working of the brain, for e.g., maximizing cognition while minimizing the cost of supporting cognition. This allows us to extract the missing relationships by using RL to optimize an objective (reward) function that captures the above criteria. We use our model consisting of DEs (as a simulator) and the trained RL agent to predict individualized 10-year AD progression using baseline (year 0) features on synthetic and real data. The model was comparable or better at predicting 10-year cognition trajectories than state-of-the-art learning-based models. Our interpretable model demonstrated, and provided insights into, recovery/compensatory processes that mitigate the effect of AD, even though those processes were not explicitly encoded in the model. Our framework combines DEs with RL for modelling AD progression and has broad applicability for understanding other neurological disorders.
Longitudinal imaging is capable of capturing the static ana-to-mi-cal structures and the dynamic changes of the morphology resulting from aging or disease progression. Self-supervised learning allows to learn new representation from available large unlabelled data without any expert knowledge. We propose a deep learning self-supervised approach to model disease progression from longitudinal retinal optical coherence tomography (OCT). Our self-supervised model takes benefit from a generic time-related task, by learning to estimate the time interval between pairs of scans acquired from the same patient. This task is (i) easy to implement, (ii) allows to use irregularly sampled data, (iii) is tolerant to poor registration, and (iv) does not rely on additional annotations. This novel method learns a representation that focuses on progression specific information only, which can be transferred to other types of longitudinal problems. We transfer the learnt representation to a clinically highly relevant task of predicting the onset of an advanced stage of age-related macular degeneration within a given time interval based on a single OCT scan. The boost in prediction accuracy, in comparison to a network learned from scratch or transferred from traditional tasks, demonstrates that our pretrained self-supervised representation learns a clinically meaningful information.
Modeling a systems temporal behaviour in reaction to external stimuli is a fundamental problem in many areas. Pure Machine Learning (ML) approaches often fail in the small sample regime and cannot provide actionable insights beyond predictions. A promising modification has been to incorporate expert domain knowledge into ML models. The application we consider is predicting the progression of disease under medications, where a plethora of domain knowledge is available from pharmacology. Pharmacological models describe the dynamics of carefully-chosen medically meaningful variables in terms of systems of Ordinary Differential Equations (ODEs). However, these models only describe a limited collection of variables, and these variables are often not observable in clinical environments. To close this gap, we propose the latent hybridisation model (LHM) that integrates a system of expert-designed ODEs with machine-learned Neural ODEs to fully describe the dynamics of the system and to link the expert and latent variables to observable quantities. We evaluated LHM on synthetic data as well as real-world intensive care data of COVID-19 patients. LHM consistently outperforms previous works, especially when few training samples are available such as at the beginning of the pandemic.
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