Spatially informed cell-type deconvolution for spatial transcriptomics

Y Ma, X Zhou - Nature biotechnology, 2022 - nature.com
Nature biotechnology, 2022nature.com
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-based 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 …
Abstract
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-based 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 to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an 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.
nature.com