SpaDiff: Denoising for Sequence-based Spatial Transcriptomics via Diffusion Process

Spatial transcriptomics enables transcriptome-scale analysis with spatial resolution but suffers from spot-swapping, where RNA molecules drift from their true locations, introducing noise and reducing spatial specificity. We introduce SpaDiff, a denoising method that treats spot-swapping as a diffusion process. SpaDiff simulates the displacement of RNA molecules and reverses it to restore their original spatial distribution while preserving molecular counts. Evaluations on simulated and real data demonstrate that SpaDiff enhances spatial specificity of gene expression, improves data integrity, and supports more accurate downstream analyses such as clustering and spatial domain identification.