# MIRROR: Multi-Modal Pathological Self-Supervised Representation Learning via Modality Alignment and Retention

arXiv: https://arxiv.org/abs/2503.00374 · HTML: https://mlsanity.com/paper/2503.00374/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 42 of its 97 references that are in the map.
- First posted on arXiv 1 Mar 2025.

## Builds on (most cited first, 30 of 42)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [Momentum Contrast for Unsupervised Visual Representation Learning](https://mlsanity.com/paper/1911.05722/) (2019)
- [Masked Autoencoders Are Scalable Vision Learners](https://mlsanity.com/paper/2111.06377/) (2021)
- [Flamingo: a Visual Language Model for Few-Shot Learning](https://mlsanity.com/paper/2204.14198/) (2022)
- [Scaling Up Visual and Vision-Language Representation Learning With Noisy Text Supervision](https://mlsanity.com/paper/2102.05918/) (2021)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [Unsupervised Learning of Visual Features by Contrasting Cluster Assignments](https://mlsanity.com/paper/2006.09882/) (2020)
- [BEiT: BERT Pre-Training of Image Transformers](https://mlsanity.com/paper/2106.08254/) (2021)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [LLaVA-Med: Training a Large Language-and-Vision Assistant for Biomedicine in One Day](https://mlsanity.com/paper/2306.00890/) (2023)
- [CoCa: Contrastive Captioners are Image-Text Foundation Models](https://mlsanity.com/paper/2205.01917/) (2022)
- [Deep Variational Information Bottleneck](https://mlsanity.com/paper/1612.00410/) (2016)
- [iBOT: Image BERT Pre-Training with Online Tokenizer](https://mlsanity.com/paper/2111.07832/) (2021)
- [MedCLIP: Contrastive Learning from Unpaired Medical Images and Text](https://mlsanity.com/paper/2210.10163/) (2022)
- [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)
- [Sensitivity and Generalization in Neural Networks: an Empirical Study](https://mlsanity.com/paper/1802.08760/) (2018)
- [Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis](https://mlsanity.com/paper/1912.08937/) (2019)
- [Self supervised contrastive learning for digital histopathology](https://mlsanity.com/paper/2011.13971/) (2020)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [Virchow: A Million-Slide Digital Pathology Foundation Model](https://mlsanity.com/paper/2309.07778/) (2023)
- [Self-Path: Self-supervision for Classification of Pathology Images with Limited Annotations](https://mlsanity.com/paper/2008.05571/) (2020)

## Built on by (most cited first, 3 of 3)

- [Gene-DML: Dual-Pathway Multi-Level Discrimination for Gene Expression Prediction from Histopathology Images](https://mlsanity.com/paper/2507.14670/) (2025)
- [RNA-FM: Flow-Matching Generative Model for Genome-wide RNA-Seq Prediction](https://mlsanity.com/paper/2605.11622/) (2026)
- [Synergistic Information Disentanglement for Omni-modal Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2609.02118/) (2026)

## Abstract (arXiv)

Histopathology and transcriptomics are fundamental modalities in oncology, encapsulating the morphological and molecular aspects of the disease. Multi-modal self-supervised learning has demonstrated remarkable potential in learning pathological representations by integrating diverse data sources. Conventional multi-modal integration methods primarily emphasize modality alignment, while paying insufficient attention to retaining the modality-specific structures. However, unlike conventional scenarios where multi-modal inputs share highly overlapping features, histopathology and transcriptomics exhibit pronounced heterogeneity, offering orthogonal yet complementary insights. Histopathology provides morphological and spatial context, elucidating tissue architecture and cellular topology, whereas transcriptomics delineates molecular signatures through gene expression patterns. This inherent disparity introduces a major challenge in aligning them while maintaining modality-specific fidelity. To address these challenges, we present MIRROR, a novel multi-modal representation learning method designed to foster both modality alignment and retention. MIRROR employs dedicated encoders to extract comprehensive features for each modality, which is further complemented by a modality alignment module to achieve seamless integration between phenotype patterns and molecular profiles. Furthermore, a modality retention module safeguards unique attributes from each modality, while a style clustering module mitigates redundancy and enhances disease-relevant information by modeling and aligning consistent pathological signatures within a clustering space. Extensive evaluations on TCGA cohorts for cancer subtyping and survival analysis highlight MIRROR's superior performance, demonstrating its effectiveness in constructing comprehensive oncological feature representations and benefiting the cancer diagnosis.