Reference-free cell-type deconvolution of pixel-resolution spatially resolved transcriptomics data

Abstract Recent technological advancements have enabled spatially resolved transcriptomic profiling but at multi-cellular pixel resolution, thereby hindering the identification of cell-type spatial co-localization patterns. We developed STdeconvolve as an unsupervised approach to deconvolve underlying cell-types comprising such multi-cellular pixel resolution spatially resolved transcriptomics datasets. We show that STdeconvolve effectively recovers the putative transcriptomic profiles of cell-types and their proportional representation within spatially resolved pixels without reliance on external single-cell transcriptomics references.