# Masked Omics Modeling for Multimodal Representation Learning across Histopathology and Molecular Profiles

arXiv: https://arxiv.org/abs/2508.00969 · HTML: https://mlsanity.com/paper/2508.00969/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 29 of its 52 references that are in the map.
- First posted on arXiv 1 Aug 2025.

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

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Masked Autoencoders Are Scalable Vision Learners](https://mlsanity.com/paper/2111.06377/) (2021)
- [Emerging Properties in Self-Supervised Vision Transformers](https://mlsanity.com/paper/2104.14294/) (2021)
- [Deep Sets](https://mlsanity.com/paper/1703.06114/) (2017)
- [Perceiver: General Perception with Iterative Attention](https://mlsanity.com/paper/2103.03206/) (2021)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [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)
- [MultiMAE: Multi-modal Multi-task Masked Autoencoders](https://mlsanity.com/paper/2204.01678/) (2022)
- [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)
- [4M: Massively Multimodal Masked Modeling](https://mlsanity.com/paper/2312.06647/) (2023)
- [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)
- [A Scalable Discrete-Time Survival Model for Neural Networks](https://mlsanity.com/paper/1805.00917/) (2018)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [Continuous and Discrete-Time Survival Prediction with Neural Networks](https://mlsanity.com/paper/1910.06724/) (2019)
- [Molecular-driven Foundation Model for Oncologic Pathology](https://mlsanity.com/paper/2501.16652/) (2025)
- [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)
- [Stability of clinical prediction models developed using statistical or machine learning methods](https://mlsanity.com/paper/2211.01061/) (2022)
- [Masked Pre-Training of Transformers for Histology Image Analysis](https://mlsanity.com/paper/2304.07434/) (2023)
- [DRIM: Learning Disentangled Representations from Incomplete Multimodal Healthcare Data](https://mlsanity.com/paper/2409.17055/) (2024)
- [Self-Supervision Enhances Instance-based Multiple Instance Learning Methods in Digital Pathology: A Benchmark Study](https://mlsanity.com/paper/2505.01109/) (2025)
- [Uncovering the Genetic Basis of Glioblastoma Heterogeneity through Multimodal Analysis of Whole Slide Images and RNA Sequencing Data](https://mlsanity.com/paper/2410.18710/) (2024)

## Abstract (arXiv)

Self-supervised learning (SSL) has driven major advances in computational pathology by enabling the learning of rich representations from histopathology data. Yet, tissue analysis alone may fall short in capturing broader molecular complexity, as key complementary information resides in high-dimensional omics profiles such as transcriptomics, methylomics, and genomics. To address this gap, we introduce MORPHEUS, the first multimodal pre-training strategy that integrates histopathology images and multi-omics data within a shared transformer-based architecture. At its core, MORPHEUS relies on a novel masked omics modeling objective that encourages the model to learn meaningful cross-modal relationships. This yields a general-purpose pre-trained encoder that can be applied to histopathology alone or in combination with any subset of omics modalities. Beyond inference, MORPHEUS also supports flexible any-to-any omics reconstruction, enabling one or more omics profiles to be reconstructed from any modality subset that includes histopathology. Pre-trained on a large pan-cancer cohort, MORPHEUS shows substantial improvements over supervised and SSL baselines across diverse tasks and modality combinations. Together, these capabilities position it as a promising direction for the development of multimodal foundation models in oncology. Code is publicly available at https://github.com/Lucas-rbnt/MORPHEUS