SDePER (Spatial Deconvolution method with Platform Effect Removal) is a hybrid machine learning and regression method to deconvolve Spatial barcoding-based transcriptomic data using reference single-cell RNA sequencing data, considering platform effects removal, sparsity of cell types per capture spot and across-spots spatial correlation in cell type compositions. SDePER is also able to impute cell type compositions and gene expression at unmeasured locations in a tissue map with enhanced resolution.