# Prototype Learning to Create Refined Interpretable Digital Phenotypes from ECGs

arXiv: https://arxiv.org/abs/2508.01521 · HTML: https://mlsanity.com/paper/2508.01521/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 5 of its 19 references that are in the map.
- First posted on arXiv 2 Aug 2025.

## Builds on (most cited first, 5 of 5)

- [This Looks Like That: Deep Learning for Interpretable Image Recognition](https://mlsanity.com/paper/1806.10574/) (2018)
- [ScispaCy: Fast and Robust Models for Biomedical Natural Language Processing](https://mlsanity.com/paper/1902.07669/) (2019)
- [IAIA-BL: A Case-based Interpretable Deep Learning Model for Classification of Mass Lesions in Digital Mammography](https://mlsanity.com/paper/2103.12308/) (2021)
- [Improving Clinician Performance in Classification of EEG Patterns on the Ictal-Interictal-Injury Continuum using Interpretable Machine Learning](https://mlsanity.com/paper/2211.05207/) (2022)
- [ProtoECGNet: Case-Based Interpretable Deep Learning for Multi-Label ECG Classification with Contrastive Learning](https://mlsanity.com/paper/2504.08713/) (2025)

## Abstract (arXiv)

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.