Ziyang Song

In the healthcare domain, time-series data are often irregularly sampled with varying intervals through outpatient visits, posing challenges for existing models designed for equally spaced sequential data. To address this, we propose Trajectory Generative Pre-trained Transformer (TrajGPT) for representation learning on irregularly-sampled healthcare time series. TrajGPT introduces a novel Selective Recurrent Attention (SRA) module that leverages a data-dependent decay to adaptively filter irrelevant past information. As a discretized ordinary differential equation (ODE) framework, TrajGPT captures underlying continuous dynamics and enables a time-specific inference for forecasting arbitrary target timesteps without auto-regressive prediction. Experimental results based on the longitudinal EHR data PopHR from Montreal health system and eICU from PhysioNet showcase TrajGPT's superior zero-shot performance in disease forecasting, drug usage prediction, and sepsis detection. The inferred trajectories of diabetic and cardiac patients reveal meaningful comorbidity conditions, underscoring TrajGPT as a useful tool for forecasting patient health evolution.

Automatic subphenotyping from electronic health records (EHRs) provides numerous opportunities to understand diseases with unique subgroups and enhance personalized medicine for patients. However, existing machine learning algorithms either focus on specific diseases for better interpretability or produce coarse-grained phenotype topics without considering nuanced disease patterns. In this study, we propose a guided topic model, MixEHR-Nest, to infer subphenotype topics from thousands of disease using multi-modal EHR data. Specifically, MixEHR-Nest detects multiple subtopics from each phenotype topic, whose prior is guided by the expert-curated phenotype concepts such as Phenotype Codes (PheCodes) or Clinical Classification Software (CCS) codes. We evaluated MixEHR-Nest on two EHR datasets: (1) the MIMIC-III dataset; (2) the healthcare administrative database PopHR. Experimental results demonstrate that MixEHR-Nest can identify subphenotypes with distinct patterns within each phenotype, which are predictive for disease progression and severity. The MixEHR-Nest software is available at GitHub: https://github.com/li-lab-mcgill/MixEHR-Nest.

Motivation: Large-scale pre-trained models (PTMs) such as BERT and GPT have recently achieved great success in Natural Language Processing and Computer Vision domains. However, the development of PTMs on healthcare time-series data is lagging behind. This underscores the limitations of the existing transformer-based architectures, particularly their scalability to handle large-scale time series and ability to capture long-term temporal dependencies. Methods: In this study, we present Timely Generative Pre-trained Transformer (TimelyGPT). TimelyGPT employs an extrapolatable position (xPos) embedding to encode trend and periodic patterns into time-series representations. It also integrates recurrent attention and temporal convolution modules to effectively capture global-local temporal dependencies. Materials: We evaluated TimelyGPT on two large-scale healthcare time series datasets corresponding to continuous biosignals and irregularly-sampled time series, respectively: (1) the Sleep EDF dataset consisting of over 1.2 billion timesteps; (2) the longitudinal healthcare administrative database PopHR, comprising 489,000 patients randomly sampled from the Montreal population. Results: In forecasting continuous biosignals, TimelyGPT achieves accurate extrapolation up to 6,000 timesteps of body temperature during the sleep stage transition, given a short look-up window (i.e., prompt) containing only 2,000 timesteps. For irregularly-sampled time series, TimelyGPT with a proposed time-specific inference demonstrates high top recall scores in predicting future diagnoses using early diagnostic records, effectively handling irregular intervals between clinical records. Together, we envision TimelyGPT to be useful in various health domains, including long-term patient health state forecasting and patient risk trajectory prediction. Availability: The open-sourced code is available at Github.