Spatially Informed Cell Type Deconvolution for Spatial Transcriptomics

Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types. Here, we introduce a deconvolution method, conditional autoregressive deconvolution (CARD), that combines cell type–specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. CARD can also impute cell type compositions and gene expression levels at unmeasured tissue locations, enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study, and perform deconvolution without a scRNA-seq reference. Applications to four datasets including a pancreatic cancer dataset identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity, and compartmentalization of pancreatic cancer.