Abstract:Precision medicine offers the potential to tailor treatment decisions to individual patients, yet it faces significant challenges due to the complex biases in clinical observational data and the high-dimensional nature of biological data. This study models various types of treatment assignment biases using mutual information and investigates their impact on machine learning (ML) models for counterfactual prediction and biomarker identification. Unlike traditional counterfactual benchmarks that rely on fixed treatment policies, our work focuses on modeling different characteristics of the underlying observational treatment policy in distinct clinical settings. We validate our approach through experiments on toy datasets, semi-synthetic tumor cancer genome atlas (TCGA) data, and real-world biological outcomes from drug and CRISPR screens. By incorporating empirical biological mechanisms, we create a more realistic benchmark that reflects the complexities of real-world data. Our analysis reveals that different biases lead to varying model performances, with some biases, especially those unrelated to outcome mechanisms, having minimal effect on prediction accuracy. This highlights the crucial need to account for specific biases in clinical observational data in counterfactual ML model development, ultimately enhancing the personalization of treatment decisions in precision medicine.
Abstract:We propose a deep generative approach using latent temporal processes for modeling and holistically analyzing complex disease trajectories, with a particular focus on Systemic Sclerosis (SSc). We aim to learn temporal latent representations of the underlying generative process that explain the observed patient disease trajectories in an interpretable and comprehensive way. To enhance the interpretability of these latent temporal processes, we develop a semi-supervised approach for disentangling the latent space using established medical knowledge. By combining the generative approach with medical definitions of different characteristics of SSc, we facilitate the discovery of new aspects of the disease. We show that the learned temporal latent processes can be utilized for further data analysis and clinical hypothesis testing, including finding similar patients and clustering SSc patient trajectories into novel sub-types. Moreover, our method enables personalized online monitoring and prediction of multivariate time series with uncertainty quantification.
Abstract:The identification of phenotypes within complex diseases or syndromes is a fundamental component of precision medicine, which aims to adapt healthcare to individual patient characteristics. Postoperative delirium (POD) is a complex neuropsychiatric condition with significant heterogeneity in its clinical manifestations and underlying pathophysiology. We hypothesize that POD comprises several distinct phenotypes, which cannot be directly observed in clinical practice. Identifying these phenotypes could enhance our understanding of POD pathogenesis and facilitate the development of targeted prevention and treatment strategies. In this paper, we propose an approach that combines supervised machine learning for personalized POD risk prediction with unsupervised clustering techniques to uncover potential POD phenotypes. We first demonstrate our approach using synthetic data, where we simulate patient cohorts with predefined phenotypes based on distinct sets of informative features. We aim to mimic any clinical disease with our synthetic data generation method. By training a predictive model and applying SHAP, we show that clustering patients in the SHAP feature importance space successfully recovers the true underlying phenotypes, outperforming clustering in the raw feature space. We then present a case study using real-world data from a cohort of elderly surgical patients. The results showcase the utility of our approach in uncovering clinically relevant subtypes of complex disorders like POD, paving the way for more precise and personalized treatment strategies.
Abstract:AI-driven precision oncology has the transformative potential to reshape cancer treatment by leveraging the power of AI models to analyze the interaction between complex patient characteristics and their corresponding treatment outcomes. New technological platforms have facilitated the timely acquisition of multimodal data on tumor biology at an unprecedented resolution, such as single-cell multi-omics data, making this quality and quantity of data available for data-driven improved clinical decision-making. In this work, we propose a modular machine learning framework designed for personalized counterfactual cancer treatment suggestions based on an ensemble of machine learning experts trained on diverse multi-omics technologies. These specialized counterfactual experts per technology are consistently aggregated into a more powerful expert with superior performance and can provide both confidence and an explanation of its decision. The framework is tailored to address critical challenges inherent in data-driven cancer research, including the high-dimensional nature of the data, and the presence of treatment assignment bias in the retrospective observational data. The framework is showcased through comprehensive demonstrations using data from in-vitro and in-vivo treatment responses from a cohort of patients with ovarian cancer. Our method aims to empower clinicians with a reality-centric decision-support tool including probabilistic treatment suggestions with calibrated confidence and personalized explanations for tailoring treatment strategies to multi-omics characteristics of individual cancer patients.
Abstract:We propose a new automated evaluation metric for machine-generated radiology reports using the successful COMET architecture adapted for the radiology domain. We train and publish four medically-oriented model checkpoints, including one trained on RadGraph, a radiology knowledge graph. Our results show that our metric correlates moderately to high with established metrics such as BERTscore, BLEU, and CheXbert scores. Furthermore, we demonstrate that one of our checkpoints exhibits a high correlation with human judgment, as assessed using the publicly available annotations of six board-certified radiologists, using a set of 200 reports. We also performed our own analysis gathering annotations with two radiologists on a collection of 100 reports. The results indicate the potential effectiveness of our method as a radiology-specific evaluation metric. The code, data, and model checkpoints to reproduce our findings will be publicly available.
Abstract:In this paper, we propose a deep generative time series approach using latent temporal processes for modeling and holistically analyzing complex disease trajectories. We aim to find meaningful temporal latent representations of an underlying generative process that explain the observed disease trajectories in an interpretable and comprehensive way. To enhance the interpretability of these latent temporal processes, we develop a semi-supervised approach for disentangling the latent space using established medical concepts. By combining the generative approach with medical knowledge, we leverage the ability to discover novel aspects of the disease while integrating medical concepts into the model. We show that the learned temporal latent processes can be utilized for further data analysis and clinical hypothesis testing, including finding similar patients and clustering the disease into new sub-types. Moreover, our method enables personalized online monitoring and prediction of multivariate time series including uncertainty quantification. We demonstrate the effectiveness of our approach in modeling systemic sclerosis, showcasing the potential of our machine learning model to capture complex disease trajectories and acquire new medical knowledge.
Abstract:Human genetic diseases often arise from point mutations, emphasizing the critical need for precise genome editing techniques. Among these, base editing stands out as it allows targeted alterations at the single nucleotide level. However, its clinical application is hindered by low editing efficiency and unintended mutations, necessitating extensive trial-and-error experimentation in the laboratory. To speed up this process, we present an attention-based two-stage machine learning model that learns to predict the likelihood of all possible editing outcomes for a given genomic target sequence. We further propose a multi-task learning schema to jointly learn multiple base editors (i.e. variants) at once. Our model's predictions consistently demonstrated a strong correlation with the actual experimental results on multiple datasets and base editor variants. These results provide further validation for the models' capacity to enhance and accelerate the process of refining base editing designs.
Abstract:Irregular multivariate time series data is prevalent in the clinical and healthcare domains. It is characterized by time-wise and feature-wise irregularities, making it challenging for machine learning methods to work with. To solve this, we introduce a new model architecture composed of two modules: (1) DLA, a Dynamic Local Attention mechanism that uses learnable queries and feature-specific local windows when computing the self-attention operation. This results in aggregating irregular time steps raw input within each window to a harmonized regular latent space representation while taking into account the different features' sampling rates. (2) A hierarchical MLP mixer that processes the output of DLA through multi-scale patching to leverage information at various scales for the downstream tasks. Our approach outperforms state-of-the-art methods on three real-world datasets, including the latest clinical MIMIC IV dataset.
Abstract:We propose a novel framework that combines deep generative time series models with decision theory for generating personalized treatment strategies. It leverages historical patient trajectory data to jointly learn the generation of realistic personalized treatment and future outcome trajectories through deep generative time series models. In particular, our framework enables the generation of novel multivariate treatment strategies tailored to the personalized patient history and trained for optimal expected future outcomes based on conditional expected utility maximization. We demonstrate our framework by generating personalized insulin treatment strategies and blood glucose predictions for hospitalized diabetes patients, showcasing the potential of our approach for generating improved personalized treatment strategies. Keywords: deep generative model, probabilistic decision support, personalized treatment generation, insulin and blood glucose prediction
Abstract:Current transformer-based models achieved great success in generating radiology reports from chest X-ray images. Nonetheless, one of the major issues is the model's lack of prior knowledge, which frequently leads to false references to non-existent prior exams in synthetic reports. This is mainly due to the knowledge gap between radiologists and the generation models: radiologists are aware of the prior information of patients to write a medical report, while models only receive X-ray images at a specific time. To address this issue, we propose a novel approach that employs a labeler to extract comparison prior information from radiology reports in the IU X-ray and MIMIC-CXR datasets. This comparison prior is then incorporated into state-of-the-art transformer-based models, allowing them to generate more realistic and comprehensive reports. We test our method on the IU X-ray and MIMIC-CXR datasets and find that it outperforms previous state-of-the-art models in terms of both automatic and human evaluation metrics. In addition, unlike previous models, our model generates reports that do not contain false references to non-existent prior exams. Our approach provides a promising direction for bridging the gap between radiologists and generation models in medical report generation.