GROVER融合多组学与病理图像,自适应对齐空间数据提升疾病分析精度。
GROVER: Graph-guided Representation of Omics and Vision with Expert Regulation for Adaptive Spatial Multi-omics Fusion
- 用图神经网络捕捉组学与空间结构的非线性关系,生成高表达嵌入。
- 通过斑点级对比学习实现跨模态精准对齐,解决分辨率差异问题。
- 动态专家路由机制自动筛选高质量信号,适合生物医学多模态研究者。
有效建模多模态空间组学数据对于理解组织复杂性和潜在生物学机制至关重要。尽管空间转录组、蛋白质组和表观遗传组捕获分子特征,但缺乏病理形态学背景。将这些组学数据与组织病理图像整合,是全面分析疾病组织的关键。然而,组学、影像与空间模态间存在显著异质性,语义不同的数据简单融合常导致模糊表示。此外,高分辨率病理图像与低分辨率测序斑点之间的分辨率不匹配加剧了空间对齐难度。样本制备过程中的生物扰动进一步扭曲模态特异性信号,阻碍准确整合。为此,我们提出图引导的组学与视觉自适应空间多组学融合框架(GROVER)。GROVER基于科尔莫戈罗夫-阿诺德网络构建图卷积编码器,捕捉各模态与其关联空间结构间的非线性依赖,生成具有表现力的模态专属嵌入。为对齐这些表示,我们引入斑点-特征对对比学习策略,在每个斑点层面显式优化跨模态对应关系。此外,设计动态专家路由机制,自适应选择每个斑点的有用模态,抑制噪声或低质量输入。在真实世界空间组学数据集上的实验表明,GROVER优于现有最先进基线,提供了一种稳健可靠的多模态整合解决方案。
原文摘要 · Abstract (English)
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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