MixEHR-Nest: Identifying Subphenotypes within Electronic Health Records through Hierarchical Guided-Topic Modeling

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.