# Disentangled Multi-modal Learning of Histology and Transcriptomics for Cancer Characterization

arXiv: https://arxiv.org/abs/2508.16479 · HTML: https://mlsanity.com/paper/2508.16479/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 27 of its 55 references that are in the map.
- First posted on arXiv 22 Aug 2025.

## Builds on (most cited first, 27 of 27)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Distilling the Knowledge in a Neural Network](https://mlsanity.com/paper/1503.02531/) (2015)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [DynamicViT: Efficient Vision Transformers with Dynamic Token Sparsification](https://mlsanity.com/paper/2106.02034/) (2021)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Self-Normalizing Neural Networks](https://mlsanity.com/paper/1706.02515/) (2017)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Vision Transformer with Deformable Attention](https://mlsanity.com/paper/2201.00520/) (2022)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis](https://mlsanity.com/paper/1912.08937/) (2019)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction](https://mlsanity.com/paper/2306.08330/) (2023)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [Cross-Modal Translation and Alignment for Survival Analysis](https://mlsanity.com/paper/2309.12855/) (2023)
- [Dynamic Graph Representation with Knowledge-aware Attention for Histopathology Whole Slide Image Analysis](https://mlsanity.com/paper/2403.07719/) (2024)
- [Histopathology Whole Slide Image Analysis with Heterogeneous Graph Representation Learning](https://mlsanity.com/paper/2307.04189/) (2023)
- [Multimodal Prototyping for cancer survival prediction](https://mlsanity.com/paper/2407.00224/) (2024)
- [Prototypical Information Bottlenecking and Disentangling for Multimodal Cancer Survival Prediction](https://mlsanity.com/paper/2401.01646/) (2024)
- [MoME: Mixture of Multimodal Experts for Cancer Survival Prediction](https://mlsanity.com/paper/2406.09696/) (2024)
- [Robust Multimodal Survival Prediction with the Latent Differentiation Conditional Variational AutoEncoder](https://mlsanity.com/paper/2503.09496/) (2025)
- [Multi-task Learning of Histology and Molecular Markers for Classifying Diffuse Glioma](https://mlsanity.com/paper/2303.14845/) (2023)
- [Multimodal Cancer Survival Analysis via Hypergraph Learning with Cross-Modality Rebalance](https://mlsanity.com/paper/2505.11997/) (2025)
- [Knowledge-driven Subspace Fusion and Gradient Coordination for Multi-modal Learning](https://mlsanity.com/paper/2406.13979/) (2024)
- [Memory-Augmented Incomplete Multimodal Survival Prediction via Cross-Slide and Gene-Attentive Hypergraph Learning](https://mlsanity.com/paper/2506.19324/) (2025)
- [Focus on Focus: Focus-oriented Representation Learning and Multi-view Cross-modal Alignment for Glioma Grading](https://mlsanity.com/paper/2408.08527/) (2024)

## Built on by (most cited first, 2 of 2)

- [Momentum Memory for Knowledge Distillation in Computational Pathology](https://mlsanity.com/paper/2602.21395/) (2026)
- [Pathway-Structured Privileged Distillation for Deployable Computational Pathology](https://mlsanity.com/paper/2606.02877/) (2026)

## Abstract (arXiv)

Histopathology remains the gold standard for cancer diagnosis and prognosis. With the advent of transcriptome profiling, multi-modal learning combining transcriptomics with histology offers more comprehensive information. However, existing multi-modal approaches are challenged by intrinsic multi-modal heterogeneity, insufficient multi-scale integration, and reliance on paired data, restricting clinical applicability. To address these challenges, we propose a disentangled multi-modal framework with four contributions: 1) To mitigate multi-modal heterogeneity, we decompose WSIs and transcriptomes into tumor and microenvironment subspaces using a disentangled multi-modal fusion module, and introduce a confidence-guided gradient coordination strategy to balance subspace optimization. 2) To enhance multi-scale integration, we propose an inter-magnification gene-expression consistency strategy that aligns transcriptomic signals across WSI magnifications. 3) To reduce dependency on paired data, we propose a subspace knowledge distillation strategy enabling transcriptome-agnostic inference through a WSI-only student model. 4) To improve inference efficiency, we propose an informative token aggregation module that suppresses WSI redundancy while preserving subspace semantics. Extensive experiments on cancer diagnosis, prognosis, and survival prediction demonstrate our superiority over state-of-the-art methods across multiple settings. Code is available at https://github.com/helenypzhang/Disentangled-Multimodal-Learning.