SAMGTD: Spatial-Aware Masked Graph Transformer-Diffusion Model for Enhanced Cell Type Deconvolution in Spatial Transcriptomics

Recent advances in spatial transcriptomics have enabled the integration of gene expression profiles with precise spatial coordinates, which have facilitated the exploration of tumor occurrence and development mechanisms, as well as the development of more effective targeted and immunotherapy approaches for tumor treatment. Deciphering cell type represents a critical challenge in spatial transcriptomics research. Existing methods are limited by the pervasive “dropout” events in spatial transcriptomics, hindering their ability to fully capture the relationship between spatial location and gene expression, thereby compromising the performance of cell type deconvolution. To address these limitations, we propose a spatial-aware masked graph transformer-diffusion model (SAMGTD) for enhanced cell type deconvolution in spatial transcriptomics. For spatial transcriptomics, the masked graph transformer model is designed to adaptively capture complex dependencies between spatial locations and gene expression. It employs a masking strategy that guides the model to focus on important local information during training, while the multi-head attention mechanism captures global context. More importantly, the spatial diffusion model is constructed to achieve the dual enhancement of spatial transcriptomics, including denoising and data imputation. It incorporates the multi-head attention mechanism and residual blocks, effectively addressing the “dropout” issue commonly encountered in spatial transcriptomics. For scRNA-seq, we construct a variational autoencoder to reduce noise interference while preserving key gene expression information. Finally, we construct a spatial-aware contrastive learning model to integrate scRNA-seq and spatial transcriptomics for cell type deconvolution. Experiments conducted on three datasets demonstrate that SAMGTD outperforms baseline methods.