# PA-MIL: Phenotype-Aware Multiple Instance Learning Guided by Language Prompting and Genotype-to-Phenotype Relationships

arXiv: https://arxiv.org/abs/2602.02558 · HTML: https://mlsanity.com/paper/2602.02558/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 29 of its 51 references that are in the map.
- First posted on arXiv 30 Jan 2026.

## Builds on (most cited first, 29 of 29)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Concept Bottleneck Models](https://mlsanity.com/paper/2007.04612/) (2020)
- [Contrastive Representation Distillation](https://mlsanity.com/paper/1910.10699/) (2019)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [BiomedCLIP: a multimodal biomedical foundation model pretrained from fifteen million scientific image-text pairs](https://mlsanity.com/paper/2303.00915/) (2023)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Whole Slide Images are 2D Point Clouds: Context-Aware Survival Prediction using Patch-based Graph Convolutional Networks](https://mlsanity.com/paper/2107.13048/) (2021)
- [Do Concept Bottleneck Models Learn as Intended?](https://mlsanity.com/paper/2105.04289/) (2021)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [A graph-transformer for whole slide image classification](https://mlsanity.com/paper/2205.09671/) (2022)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model](https://mlsanity.com/paper/2407.15362/) (2024)
- [Additive MIL: Intrinsically Interpretable Multiple Instance Learning for Pathology](https://mlsanity.com/paper/2206.01794/) (2022)
- [Histopathology Whole Slide Image Analysis with Heterogeneous Graph Representation Learning](https://mlsanity.com/paper/2307.04189/) (2023)
- [DGMIL: Distribution Guided Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2206.08861/) (2022)
- [Handcrafted Histological Transformer (H2T): Unsupervised Representation of Whole Slide Images](https://mlsanity.com/paper/2202.07001/) (2022)
- [WsiCaption: Multiple Instance Generation of Pathology Reports for Gigapixel Whole-Slide Images](https://mlsanity.com/paper/2311.16480/) (2023)
- [Generalizable Whole Slide Image Classification with Fine-Grained Visual-Semantic Interaction](https://mlsanity.com/paper/2402.19326/) (2024)
- [SI-MIL: Taming Deep MIL for Self-Interpretability in Gigapixel Histopathology](https://mlsanity.com/paper/2312.15010/) (2023)
- [CAMIL: Context-Aware Multiple Instance Learning for Cancer Detection and Subtyping in Whole Slide Images](https://mlsanity.com/paper/2305.05314/) (2023)
- [Rethinking Transformer for Long Contextual Histopathology Whole Slide Image Analysis](https://mlsanity.com/paper/2410.14195/) (2024)
- [SCMIL: Sparse Context-aware Multiple Instance Learning for Predicting Cancer Survival Probability Distribution in Whole Slide Images](https://mlsanity.com/paper/2407.00664/) (2024)
- [Label-free Concept Based Multiple Instance Learning for Gigapixel Histopathology](https://mlsanity.com/paper/2501.02922/) (2025)
- [Cells are Actors: Social Network Analysis with Classical ML for SOTA Histology Image Classification](https://mlsanity.com/paper/2106.15299/) (2021)

## Abstract (arXiv)

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.