用双层超球空间建模组织基因表达,提升显微图像预测精度。
HyperST: Hierarchical Hyperbolic Learning for Spatial Transcriptomics Prediction
- 在超球几何空间中分层建模图像与基因数据的结构关系。
- 在四个组织数据集上达到当前最优预测性能。
- 适合需要跨模态对齐的生物医学图像分析研究者。
空间转录组学(ST)结合病理图像与基因表达信息,将分子特征与组织结构关联,实现斑点级功能分析。从组织切片图像预测基因表达是替代昂贵ST技术的低成本方案。现有方法多聚焦斑点级图像-基因匹配,未能利用数据的完整层次结构,尤其在基因表达层面,导致图像-基因对齐不充分。此外,存在固有信息不对称:基因表达包含更多分子细节,但在显微图像中可能缺乏显著视觉对应,需复杂表征学习以弥合模态差距。我们提出HyperST框架,通过在超球空间建模数据内在层次结构,学习多层级图像-基因表示。首先设计多层级表征提取器,从各模态捕捉斑点级与微环境级表征,提供超越单个斑点对的上下文信息。其次引入分层超球对齐模块,统一表征并完成空间对齐,同时层次化构建图像与基因嵌入。该策略使图像表征融合分子语义,显著提升跨模态预测效果。HyperST在四个不同组织的公开数据集上达到最先进性能,为更高效、精准的空间转录组预测铺平道路。
原文摘要 · Abstract (English)
Spatial Transcriptomics (ST) merges the benefits of pathology images and gene expression, linking molecular profiles with tissue structure to analyze spot-level function comprehensively. Predicting gene expression from histology images is a cost-effective alternative to expensive ST technologies. However, existing methods mainly focus on spot-level image-to-gene matching but fail to leverage the full hierarchical structure of ST data, especially on the gene expression side, leading to incomplete image-gene alignment. Moreover, a challenge arises from the inherent information asymmetry: gene expression profiles contain more molecular details that may lack salient visual correlates in histological images, demanding a sophisticated representation learning approach to bridge this modality gap. We propose HyperST, a framework for ST prediction that learns multi-level image-gene representations by modeling the data's inherent hierarchy within hyperbolic space, a natural geometric setting for such structures. First, we design a Multi-Level Representation Extractors to capture both spot-level and niche-level representations from each modality, providing context-aware information beyond individual spot-level image-gene pairs. Second, a Hierarchical Hyperbolic Alignment module is introduced to unify these representations, performing spatial alignment while hierarchically structuring image and gene embeddings. This alignment strategy enriches the image representations with molecular semantics, significantly improving cross-modal prediction. HyperST achieves state-of-the-art performance on four public datasets from different tissues, paving the way for more scalable and accurate spatial transcriptomics prediction.
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