LETSmix: a spatially informed and learning-based domain adaptation method for cell-type deconvolution in spatial transcriptomics

Spatial transcriptomics (ST) enables the study of gene expression in spatial context, but many ST technologies face challenges due to limited resolution, leading to cell mixtures at each spot. We present LETSmix to deconvolve cell types by integrating spatial correlations through a tailored LETS filter, which leverages layer annotations, expression similarities, image texture features, and spatial coordinates to refine ST data. Additionally, LETSmix employs a mixup-augmented domain adaptation strategy to address discrepancies between ST and reference single-cell RNA sequencing data. Comprehensive evaluations across diverse ST platforms and tissue types demonstrate its high accuracy in estimating cell-type proportions and spatial patterns, surpassing existing methods (URL: https://github.com/ZhanYangen/LETSmix).