用图像建图模型,跨切片预测基因表达,更准且有生物意义。
Cross-Slice Knowledge Transfer via Masked Multi-Modal Heterogeneous Graph Contrastive Learning for Spatial Gene Expression Inference
- 构建异质图,融合单切片内与多切片间关系。
- 在7个数据集上超越9种主流方法,提升显著。
- 适合病理与基因联合分析的研究者使用。
空间转录组学(ST)虽深化了我们对组织中基因表达的理解,但其高昂的实验成本限制了大规模应用。通过病理图像预测ST是一种低成本替代方案,但现有方法难以捕捉跨切片的复杂空间关系。为此,我们提出SpaHGC,一种基于多模态异质图的模型,从组织学图像中同时捕捉目标切片内的点-点关系及跨切片的相似性。该模型利用病理基础模型提取的图像嵌入实现切片间知识迁移,并引入掩码图对比学习,增强特征表示,使空间基因表达知识得以有效传递。在来自不同平台、组织类型和癌症亚型的7个匹配的组织学-空间转录组数据集上进行全面基准测试,结果表明SpaHGC在所有评估指标上均显著优于9种现有最先进方法。此外,预测结果在多个癌症相关通路中显著富集,凸显其强大的生物学相关性与应用潜力。
原文摘要 · Abstract (English)
While spatial transcriptomics (ST) has advanced our understanding of gene expression in tissue context, its high experimental cost limits its large-scale application. Predicting ST from pathology images is a promising, cost-effective alternative, but existing methods struggle to capture complex cross-slide spatial relationships. To address the challenge, we propose SpaHGC, a multi-modal heterogeneous graph-based model that captures both intra-slice and inter-slice spot-spot relationships from histology images. It integrates local spatial context within the target slide and cross-slide similarities computed from image embeddings extracted by a pathology foundation model. These embeddings enable inter-slice knowledge transfer, and SpaHGC further incorporates Masked Graph Contrastive Learning to enhance feature representation and transfer spatial gene expression knowledge from reference to target slides, enabling it to model complex spatial dependencies and significantly improve prediction accuracy. We conducted comprehensive benchmarking on seven matched histology-ST datasets from different platforms, tissues, and cancer subtypes. The results demonstrate that SpaHGC significantly outperforms the existing nine state-of-the-art methods across all evaluation metrics. Additionally, the predictions are significantly enriched in multiple cancer-related pathways, thereby highlighting its strong biological relevance and application potential.
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