GR2ST: Spatial Transcriptomics Prediction Based on Graph-Enhanced Multimodal Contrastive Learning

Motivation Spatial transcriptomics techniques capture gene expression data and spatial coordinates, while simultaneously correlating them with tissue section images. This advantage makes Spatial transcriptomics data highly valuable for research, such as investigating disease mechanisms and cancer prognosis. However, the extended time and high cost of spatial transcriptomic sequencing currently limit further advancements in this field. The development of numerous deep learning methods aimed at predicting spatial transcriptomics from histology images has advanced significantly. However, these approaches often lack the ability to effectively integrate histology images with spatial transcriptomic data. Here, we propose GR2ST, a deep learning model that learns the underlying connections between image features and gene expression to predict spatial transcriptomics.Results GR2ST leverages a large pre-trained pathology model to extract high-level histological features. We designed a dual-branch graph architecture, consisting of a dynamic threshold-based functional graph and a radius-constrained spatial graph, to capture complex spot interactions within heterogeneous tissues. The model aligns histology images with gene expression representations through a multimodal contrastive learning framework. It achieves adaptive gene expression generation via a Cell-Type Guided Multi-Branch Regression Head supervised by a context-aware weighting network, which is further integrated with cross-sample retrieval to construct an ensemble prediction. The performance of the model is evaluated on three cancer-related spatial transcriptomics datasets, including cutaneous squamous cell carcinoma and two human breast cancer cohorts, to demonstrate its effectiveness and robustness.Availability https://github.com/zjl1109294570/GR2ST.