# Prototypical Information Bottlenecking and Disentangling for Multimodal Cancer Survival Prediction

arXiv: https://arxiv.org/abs/2401.01646 · HTML: https://mlsanity.com/paper/2401.01646/

## Key facts

- Cited by 41 papers in the map (data through 14 Oct 2026).
- Builds on 32 of its 72 references that are in the map.
- First posted on arXiv 3 Jan 2024.

## Builds on (most cited first, 30 of 32)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Learning deep representations by mutual information estimation and maximization](https://mlsanity.com/paper/1808.06670/) (2018)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Deep Variational Information Bottleneck](https://mlsanity.com/paper/1612.00410/) (2016)
- [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)
- [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)
- [CLUB: A Contrastive Log-ratio Upper Bound of Mutual Information](https://mlsanity.com/paper/2006.12013/) (2020)
- [Learning Robust Representations via Multi-View Information Bottleneck](https://mlsanity.com/paper/2002.07017/) (2020)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis](https://mlsanity.com/paper/1912.08937/) (2019)
- [Patch-based Convolutional Neural Network for Whole Slide Tissue Image Classification](https://mlsanity.com/paper/1504.07947/) (2015)
- [Stop Uploading Test Data in Plain Text: Practical Strategies for Mitigating Data Contamination by Evaluation Benchmarks](https://mlsanity.com/paper/2305.10160/) (2023)
- [Improving Multimodal Fusion with Hierarchical Mutual Information Maximization for Multimodal Sentiment Analysis](https://mlsanity.com/paper/2109.00412/) (2021)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [Multimodal Intelligence: Representation Learning, Information Fusion, and Applications](https://mlsanity.com/paper/1911.03977/) (2019)
- [Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction](https://mlsanity.com/paper/2306.08330/) (2023)
- [Cross-Modal Translation and Alignment for Survival Analysis](https://mlsanity.com/paper/2309.12855/) (2023)
- [Generalized Product of Experts for Automatic and Principled Fusion of Gaussian Process Predictions](https://mlsanity.com/paper/1410.7827/) (2014)
- [Task-specific Fine-tuning via Variational Information Bottleneck for Weakly-supervised Pathology Whole Slide Image Classification](https://mlsanity.com/paper/2303.08446/) (2023)
- [Learning Disentangled Representations via Mutual Information Estimation](https://mlsanity.com/paper/1912.03915/) (2019)
- [Multimodal Information Bottleneck: Learning Minimal Sufficient Unimodal and Multimodal Representations](https://mlsanity.com/paper/2210.17444/) (2022)
- [A Framework for Learning Ante-hoc Explainable Models via Concepts](https://mlsanity.com/paper/2108.11761/) (2021)
- [A Variational Information Bottleneck Approach to Multi-Omics Data Integration](https://mlsanity.com/paper/2102.03014/) (2021)
- [Computational Pathology: A Survey Review and The Way Forward](https://mlsanity.com/paper/2304.05482/) (2023)
- [AdvMIL: Adversarial Multiple Instance Learning for the Survival Analysis on Whole-Slide Images](https://mlsanity.com/paper/2212.06515/) (2022)
- [Learning Disentangled Representations for Counterfactual Regression via Mutual Information Minimization](https://mlsanity.com/paper/2206.01022/) (2022)
- [Do SSL Models Have D'ej`a Vu? A Case of Unintended Memorization in Self-supervised Learning](https://mlsanity.com/paper/2304.13850/) (2023)

## Built on by (most cited first, 30 of 41)

- [A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model](https://mlsanity.com/paper/2407.15362/) (2024)
- [Multimodal Prototyping for cancer survival prediction](https://mlsanity.com/paper/2407.00224/) (2024)
- [MoME: Mixture of Multimodal Experts for Cancer Survival Prediction](https://mlsanity.com/paper/2406.09696/) (2024)
- [FOCUS: Knowledge-enhanced Adaptive Visual Compression for Few-shot Whole Slide Image Classification](https://mlsanity.com/paper/2411.14743/) (2024)
- [Cohort-Individual Cooperative Learning for Multimodal Cancer Survival Analysis](https://mlsanity.com/paper/2404.02394/) (2024)
- [Robust Multimodal Survival Prediction with the Latent Differentiation Conditional Variational AutoEncoder](https://mlsanity.com/paper/2503.09496/) (2025)
- [STiL: Semi-supervised Tabular-Image Learning for Comprehensive Task-Relevant Information Exploration in Multimodal Classification](https://mlsanity.com/paper/2503.06277/) (2025)
- [Distilled Prompt Learning for Incomplete Multimodal Survival Prediction](https://mlsanity.com/paper/2503.01653/) (2025)
- [Multimodal Cancer Survival Analysis via Hypergraph Learning with Cross-Modality Rebalance](https://mlsanity.com/paper/2505.11997/) (2025)
- [Multimodal Data Integration for Precision Oncology: Challenges and Future Directions](https://mlsanity.com/paper/2406.19611/) (2024)
- [DF-DM: A foundational process model for multimodal data fusion in the artificial intelligence era](https://mlsanity.com/paper/2404.12278/) (2024)
- [SurvMamba: State Space Model with Multi-grained Multi-modal Interaction for Survival Prediction](https://mlsanity.com/paper/2404.08027/) (2024)
- [CTPD: Cross-Modal Temporal Pattern Discovery for Enhanced Multimodal Electronic Health Records Analysis](https://mlsanity.com/paper/2411.00696/) (2024)
- [SurvAgent: Hierarchical CoT-Enhanced Case Banking and Dichotomy-Based Multi-Agent System for Multimodal Survival Prediction](https://mlsanity.com/paper/2511.16635/) (2025)
- [Act Like a Pathologist: Tissue-Aware Whole Slide Image Reasoning](https://mlsanity.com/paper/2603.00667/) (2026)
- [RankByGene: Gene-Guided Histopathology Representation Learning Through Cross-Modal Ranking Consistency](https://mlsanity.com/paper/2411.15076/) (2024)
- [Disentangled and Interpretable Multimodal Attention Fusion for Cancer Survival Prediction](https://mlsanity.com/paper/2503.16069/) (2025)
- [Memory-Augmented Incomplete Multimodal Survival Prediction via Cross-Slide and Gene-Attentive Hypergraph Learning](https://mlsanity.com/paper/2506.19324/) (2025)
- [MEDFuse: Multimodal EHR Data Fusion with Masked Lab-Test Modeling and Large Language Models](https://mlsanity.com/paper/2407.12309/) (2024)
- [MIRROR: Multi-Modal Pathological Self-Supervised Representation Learning via Modality Alignment and Retention](https://mlsanity.com/paper/2503.00374/) (2025)
- [MurreNet: Modeling Holistic Multimodal Interactions Between Histopathology and Genomic Profiles for Survival Prediction](https://mlsanity.com/paper/2507.04891/) (2025)
- [PS3: A Multimodal Transformer Integrating Pathology Reports with Histology Images and Biological Pathways for Cancer Survival Prediction](https://mlsanity.com/paper/2509.20022/) (2025)
- [Multimodal Lego: Model Merging and Fine-Tuning Across Topologies and Modalities in Biomedicine](https://mlsanity.com/paper/2405.19950/) (2024)
- [Adaptive Prototype Learning for Multimodal Cancer Survival Analysis](https://mlsanity.com/paper/2503.04643/) (2025)
- [Disentangled Multi-modal Learning of Histology and Transcriptomics for Cancer Characterization](https://mlsanity.com/paper/2508.16479/) (2025)
- [A Multimodal Foundation Model to Enhance Generalizability and Data Efficiency for Pan-cancer Prognosis Prediction](https://mlsanity.com/paper/2509.12600/) (2025)
- [ME-Mamba: Multi-Expert Mamba with Efficient Knowledge Capture and Fusion for Multimodal Survival Analysis](https://mlsanity.com/paper/2509.16900/) (2025)
- [PEaRL: Pathway-Enhanced Representation Learning for Gene and Pathway Expression Prediction from Histology](https://mlsanity.com/paper/2510.03455/) (2025)
- [Distributionally Robust Alignment for Medical Federated Vision-Language Pre-training Under Data Heterogeneity](https://mlsanity.com/paper/2404.03854/) (2024)
- [Single Domain Generalization for Multimodal Cross-Cancer Prognosis via Dirac Rebalancer and Distribution Entanglement](https://mlsanity.com/paper/2507.08340/) (2025)

## Abstract (arXiv)

Multimodal learning significantly benefits cancer survival prediction, especially the integration of pathological images and genomic data. Despite advantages of multimodal learning for cancer survival prediction, massive redundancy in multimodal data prevents it from extracting discriminative and compact information: (1) An extensive amount of intra-modal task-unrelated information blurs discriminability, especially for gigapixel whole slide images (WSIs) with many patches in pathology and thousands of pathways in genomic data, leading to an ``intra-modal redundancy" issue. (2) Duplicated information among modalities dominates the representation of multimodal data, which makes modality-specific information prone to being ignored, resulting in an ``inter-modal redundancy" issue. To address these, we propose a new framework, Prototypical Information Bottlenecking and Disentangling (PIBD), consisting of Prototypical Information Bottleneck (PIB) module for intra-modal redundancy and Prototypical Information Disentanglement (PID) module for inter-modal redundancy. Specifically, a variant of information bottleneck, PIB, is proposed to model prototypes approximating a bunch of instances for different risk levels, which can be used for selection of discriminative instances within modality. PID module decouples entangled multimodal data into compact distinct components: modality-common and modality-specific knowledge, under the guidance of the joint prototypical distribution. Extensive experiments on five cancer benchmark datasets demonstrated our superiority over other methods.