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HisCMCL: Cross-Modal Contrastive Learning with Hierarchical Multi-Scale Fusion for Spatial Expression Prediction
Chengju Liu1, Fangfang Zhu2, Wenwen Min1
1School of Information Science and Engineering, Yunnan University, Yunnan 650500, China.
Bioinformatics (Oxford, England)
|May 29, 2026
Summary
HisCMCL, a multimodal framework, enhances spatial transcriptomics (ST) inference from pathology images by integrating multi-scale features and contrastive learning for improved gene expression alignment and clinical applicability.
Area of Science:
- Computational Biology
- Bioinformatics
- Medical Imaging Analysis
Background:
- High costs and complexity limit clinical use of spatial transcriptomics (ST).
- Inferring ST from pathology images is a promising alternative but faces challenges in feature alignment.
- Existing models lack multi-scale and cross-sample feature extraction, hindering generalization.
Purpose of the Study:
- To develop a novel multimodal framework for accurate spatial transcriptomics inference from pathology images.
- To address the limitations of single-scale modeling and improve feature alignment between image and gene expression data.
- To enhance the clinical applicability of spatial transcriptomics through efficient inference methods.
Main Methods:
- Proposed HisCMCL, a multimodal framework integrating multi-scale features and cross-attention.
- Fused spatial location information and employed contrastive learning for effective image and transcriptomic feature alignment.
- Evaluated the model on four public datasets to assess predictive performance.
Main Results:
- HisCMCL significantly outperforms existing baseline methods in predictive performance for spatial transcriptomics inference.
- The model demonstrates good structural consistency in identifying cancer and immune markers.
- HisCMCL effectively delineates tumor regions, providing new insights for spatial expression inference.
Conclusions:
- HisCMCL offers an effective solution for inferring spatial transcriptomics from pathology images.
- The framework's multi-scale and contrastive learning approach improves feature alignment and model generalization.
- HisCMCL shows potential for advancing cancer research and clinical diagnostics through enhanced spatial expression analysis.
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