Histopathology-Genomics Multi-modal Structural Representation Learning for Data-Efficient Precision Oncology

ICLR 2026 Conference Submission17092 Authors

Keywords: multi-modal learning, histopathology image representation learning, genomic data, graph structure learning

Abstract: Fusing histopathology images and genomics data with deep learning has significantly advanced precision oncology. However, genomics data is often missing due to its high acquisition cost and complexity in real-world clinical scenarios. Existing solutions aim to reconstruct genomics data from histopathology images. Nevertheless, these methods typically relied only on individual cases and overlooked the potential relationships among cases. Additionally, they failed to take advantage of the authentic genomics data of diagnostically related cases that are accessible from training for inference. In this work, we propose a novel Multi-modal Structural Representation Learning (MSRL) framework for data-efficient precision oncology. We pre-train a histopathology-genomics multi-modal representation graph adopting Graph Structure Learning (GSL) to construct inter-case relevance based on the data inherently. During the fine-tuning stage, we dynamically capture structural relevance between the training cases and the acquired authentic cases for precise prediction. MSRL leverages prior inter-case associations and authentic genomics data from diagnosed cases based on the graph, which contributes to effective inference based on the single histopathology image modality. We evaluated MSRL on public TCGA datasets with 7,263 cases across various tasks, including survival prediction, cancer grading, and gene mutation prediction. The results demonstrate that MSRL significantly outperforms existing missing-genomics generation approaches with improvements of 2.45% to 3.12% in C-Index on survival prediction tasks and achieves comparable performance to multi-modal fusion methods.

Primary Area: applications to computer vision, audio, language, and other modalities

Submission Number: 17092