GROVER: Graph-guided Representation of Omics and Vision with Expert Regulation for Adaptive Spatial Multi-omics Fusion

TL;DR

GROVER is a novel framework that adaptively integrates spatial multi-omics and histopathological images using graph convolutional networks, contrastive learning, and expert routing to improve tissue analysis.

Contribution

It introduces a graph-guided, adaptive fusion method with a novel routing mechanism for multimodal spatial omics data integration.

Findings

Outperforms state-of-the-art methods on real datasets.

Provides robust and reliable multimodal tissue representations.

Effectively handles heterogeneity and resolution mismatch in spatial omics data.

Abstract

Effectively modeling multimodal spatial omics data is critical for understanding tissue complexity and underlying biological mechanisms. While spatial transcriptomics, proteomics, and epigenomics capture molecular features, they lack pathological morphological context. Integrating these omics with histopathological images is therefore essential for comprehensive disease tissue analysis. However, substantial heterogeneity across omics, imaging, and spatial modalities poses significant challenges. Naive fusion of semantically distinct sources often leads to ambiguous representations. Additionally, the resolution mismatch between high-resolution histology images and lower-resolution sequencing spots complicates spatial alignment. Biological perturbations during sample preparation further distort modality-specific signals, hindering accurate integration. To address these challenges, we propose Graph-guided Representation of Omics and Vision with Expert Regulation for Adaptive Spatial Multi-omics Fusion (GROVER), a novel framework for adaptive integration of spatial multi-omics data. GROVER leverages a Graph Convolutional Network encoder based on Kolmogorov-Arnold Networks to capture the nonlinear dependencies between each modality and its associated spatial structure, thereby producing expressive, modality-specific embeddings. To align these representations, we introduce a spot-feature-pair contrastive learning strategy that explicitly optimizes the correspondence across modalities at each spot. Furthermore, we design a dynamic expert routing mechanism that adaptively selects informative modalities for each spot while suppressing noisy or low-quality inputs. Experiments on real-world spatial omics datasets demonstrate that GROVER outperforms state-of-the-art baselines, providing a robust and reliable solution for multimodal integration.