SMART: spatial transcriptomics deconvolution using marker-gene-assisted topic model

Abstract While spatial transcriptomics offer valuable insights into gene expression patterns within the spatial context of tissue, many technologies do not have a single-cell resolution. Here, we present SMART, a marker gene-assisted deconvolution method that simultaneously infers the cell type-specific gene expression profile and the cellular composition at each spot. Using multiple datasets, we show that SMART outperforms the existing methods in realistic settings. It also provides a two-stage approach to enhance its performance on cell subtypes. The covariate model of SMART enables the identification of cell type-specific differentially expressed genes across conditions, elucidating biological changes at a single-cell-type resolution.