Spatially informed graph transformers for spatially resolved transcriptomics

Spatially resolved transcriptomics (SRT) has emerged as a powerful technique for mapping gene expression landscapes within spatial contexts. However, significant challenges persist in effectively integrating gene expression with spatial information to elucidate the heterogeneity of biological tissues. Here, we present a Spatially informed Graph Transformers framework, SpaGT, which leverages both node and edge channels to model spatially aware graph representation for denoising gene expression and identifying spatial domains. Unlike conventional graph neural networks, which rely on static, localized convolutional aggregation, SpaGT employs a structure-reinforced self-attention mechanism that iteratively evolves topological structural information and transcriptional signal representation. By replacing graph convolution with global self-attention, SpaGT enables the integration of both global and spatially localized information, thereby improving the detection of fine-grained spatial domains. We demonstrate that SpaGT achieves superior performance in identifying spatial domains and denoising gene expression data across diverse platforms and species. Furthermore, SpaGT facilitates the discovery of spatially variable genes with significant prognostic potential in cancer tissues. These findings establish SpaGT as a powerful tool for unraveling the complexities of biological tissues.