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Main Authors: Sethi, Sahil, Chen, David, Burkhart, Michael C., Bhandari, Nipun, Ramadan, Bashar, Beaulieu-Jones, Brett
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2508.01521
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author Sethi, Sahil
Chen, David
Burkhart, Michael C.
Bhandari, Nipun
Ramadan, Bashar
Beaulieu-Jones, Brett
author_facet Sethi, Sahil
Chen, David
Burkhart, Michael C.
Bhandari, Nipun
Ramadan, Bashar
Beaulieu-Jones, Brett
contents Prototype-based neural networks offer interpretable predictions by comparing inputs to learned, representative signal patterns anchored in training data. While such models have shown promise in the classification of physiological data, it remains unclear whether their prototypes capture an underlying structure that aligns with broader clinical phenotypes. We use a prototype-based deep learning model trained for multi-label ECG classification using the PTB-XL dataset. Then without modification we performed inference on the MIMIC-IV clinical database. We assess whether individual prototypes, trained solely for classification, are associated with hospital discharge diagnoses in the form of phecodes in this external population. Individual prototypes demonstrate significantly stronger and more specific associations with clinical outcomes compared to the classifier's class predictions, NLP-extracted concepts, or broader prototype classes across all phecode categories. Prototype classes with mixed significance patterns exhibit significantly greater intra-class distances (p $<$ 0.0001), indicating the model learned to differentiate clinically meaningful variations within diagnostic categories. The prototypes achieve strong predictive performance across diverse conditions, with AUCs ranging from 0.89 for atrial fibrillation to 0.91 for heart failure, while also showing substantial signal for non-cardiac conditions such as sepsis and renal disease. These findings suggest that prototype-based models can support interpretable digital phenotyping from physiologic time-series data, providing transferable intermediate phenotypes that capture clinically meaningful physiologic signatures beyond their original training objectives.
format Preprint
id arxiv_https___arxiv_org_abs_2508_01521
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Prototype Learning to Create Refined Interpretable Digital Phenotypes from ECGs
Sethi, Sahil
Chen, David
Burkhart, Michael C.
Bhandari, Nipun
Ramadan, Bashar
Beaulieu-Jones, Brett
Machine Learning
Prototype-based neural networks offer interpretable predictions by comparing inputs to learned, representative signal patterns anchored in training data. While such models have shown promise in the classification of physiological data, it remains unclear whether their prototypes capture an underlying structure that aligns with broader clinical phenotypes. We use a prototype-based deep learning model trained for multi-label ECG classification using the PTB-XL dataset. Then without modification we performed inference on the MIMIC-IV clinical database. We assess whether individual prototypes, trained solely for classification, are associated with hospital discharge diagnoses in the form of phecodes in this external population. Individual prototypes demonstrate significantly stronger and more specific associations with clinical outcomes compared to the classifier's class predictions, NLP-extracted concepts, or broader prototype classes across all phecode categories. Prototype classes with mixed significance patterns exhibit significantly greater intra-class distances (p $<$ 0.0001), indicating the model learned to differentiate clinically meaningful variations within diagnostic categories. The prototypes achieve strong predictive performance across diverse conditions, with AUCs ranging from 0.89 for atrial fibrillation to 0.91 for heart failure, while also showing substantial signal for non-cardiac conditions such as sepsis and renal disease. These findings suggest that prototype-based models can support interpretable digital phenotyping from physiologic time-series data, providing transferable intermediate phenotypes that capture clinically meaningful physiologic signatures beyond their original training objectives.
title Prototype Learning to Create Refined Interpretable Digital Phenotypes from ECGs
topic Machine Learning
url https://arxiv.org/abs/2508.01521