GROVER: Graph-guided Representation of Omics and Vision with Expert Regulation for Adaptive Spatial Multi-omics Fusion
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Abstract (arXiv)
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.
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References · 4
- 2016Semi-Supervised Classification with Graph Convolutional Networkscited by 11,361
- 2018Representation Learning with Contrastive Predictive Codingcited by 7,777
- 2024PRAGA: Prototype-aware Graph Adaptive Aggregation for Spatial Multi-modal Omics Analysiscited by 5
- 2024Deep Learning in Single-Cell and Spatial Transcriptomics Data Analysis: Advances and Challenges from a Data Science Perspectivecited by 2
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- 2024Cross-modal Diffusion Modelling for Super-resolved Spatial Transcriptomics
- 2026OmicSync: Reliability-Aware Spatial Multi-Omics Clustering with Evidence-Constrained LLM Reasoning
- 2025Disentangled Multi-modal Learning of Histology and Transcriptomics for Cancer Characterization
- 2026Concept-based explanation of gene expression prediction from H&E images
- 2026Cross-Modal Knowledge Distillation from Spatial Transcriptomics to Histology
- 2024RankByGene: Gene-Guided Histopathology Representation Learning Through Cross-Modal Ranking Consistency
- 2025SIGMMA: Hierarchical Graph-Based Multi-Scale Multi-modal Contrastive Alignment of Histopathology Image and Spatial Transcriptome
- 2025C3-Diff: Super-resolving Spatial Transcriptomics via Cross-modal Cross-content Contrastive Diffusion Modelling