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| Main Authors: | , , , |
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| Format: | Preprint |
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2026
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2603.22821 |
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| _version_ | 1866914417107533824 |
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| author | Shi, Zhiceng Wang, Changmiao Wan, Jun Min, Wenwen |
| author_facet | Shi, Zhiceng Wang, Changmiao Wan, Jun Min, Wenwen |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2603_22821 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Cross-Slice Knowledge Transfer via Masked Multi-Modal Heterogeneous Graph Contrastive Learning for Spatial Gene Expression Inference Shi, Zhiceng Wang, Changmiao Wan, Jun Min, Wenwen Computer Vision and Pattern Recognition 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. |
| title | Cross-Slice Knowledge Transfer via Masked Multi-Modal Heterogeneous Graph Contrastive Learning for Spatial Gene Expression Inference |
| topic | Computer Vision and Pattern Recognition |
| url | https://arxiv.org/abs/2603.22821 |