PA-MIL: Phenotype-Aware Multiple Instance Learning Guided by Language Prompting and Genotype-to-Phenotype Relationships
This work addresses the need for more reliable and accountable explanations in cancer diagnosis from medical images, though it appears incremental as it builds on existing multiple instance learning approaches.
The paper tackles the problem of limited interpretability in deep learning for pathology whole-slide image analysis by proposing PA-MIL, a framework that identifies cancer-related phenotypes for subtyping, achieving competitive performance with improved interpretability compared to existing methods.
Deep learning has been extensively researched in the analysis of pathology whole-slide images (WSIs). However, most existing methods are limited to providing prediction interpretability by locating the model's salient areas in a post-hoc manner, failing to offer more reliable and accountable explanations. In this work, we propose Phenotype-Aware Multiple Instance Learning (PA-MIL), a novel ante-hoc interpretable framework that identifies cancer-related phenotypes from WSIs and utilizes them for cancer subtyping. To facilitate PA-MIL in learning phenotype-aware features, we 1) construct a phenotype knowledge base containing cancer-related phenotypes and their associated genotypes. 2) utilize the morphological descriptions of phenotypes as language prompting to aggregate phenotype-related features. 3) devise the Genotype-to-Phenotype Neural Network (GP-NN) grounded in genotype-to-phenotype relationships, which provides multi-level guidance for PA-MIL. Experimental results on multiple datasets demonstrate that PA-MIL achieves competitive performance compared to existing MIL methods while offering improved interpretability. PA-MIL leverages phenotype saliency as evidence and, using a linear classifier, achieves competitive results compared to state-of-the-art methods. Additionally, we thoroughly analyze the genotype-phenotype relationships, as well as cohort-level and case-level interpretability, demonstrating the reliability and accountability of PA-MIL.