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Sparse deconvolution of cell type medleys in spatial transcriptomics

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Overcoming limitations in sparse cell-type predictions for a biologically reliable task.

A, Illustration of mouse hippocampus on mouse brain coronal section. B, 2D UMAP representation of the 8 HPF cell types. C, Overlapping CA1 and CA3 due to cell type similarity, with cluster radii calculated using centroid distances and cell locations at maximum distances. D-I, Model predictions for CA3 in the P8 and J-O in adult mouse brain are presented. D, J, In DWLS prediction, CA3 cells are slightly over-represented in mouse brain spots (blue shade), with frequent spot prediction failures (red). E, K, RCTD prediction reveals high percentages of cells in spots located in hippocampal, thalamic and cortical regions. F, L, S-DWLS prediction displays confined but still disproportionate of cells in spots concentrated in stratum oriens, stratum pyramidale and stratum lucidum and thalamus regions. G, M, SPOTlight predicts a high abundance of CA3 cells in DG and across various brain zones including cortex. H, N, Stereoscope predicts CA3 in almost all hippocampus, thalamus and cortical regions, while I, O WISpR predicts CA3 cells in exactly CA3 morphological region in both P8 and adult mice, supporting its more accurate prediction on mismatched datasets.

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doi: https://doi.org/10.1371/journal.pcbi.1013169.g002