Fig. 4: A Spatially-Constrained Two-level Permutation (SCTP) test for cell–cell interaction (CCI) analysis. | Nature Communications

Fig. 4: A Spatially-Constrained Two-level Permutation (SCTP) test for cell–cell interaction (CCI) analysis.

From: Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues

Fig. 4

a Overview of the stLearn SCTP algorithm, which uses spatial location and ligand-receptor (LR) co-expression to predict interactions in multiple spatial technologies: (1) spatial neighbourhoods are scored for LR co-expression, (2) background spatial co-expression is determined by randomly pairing genes (default 1000 pairs) with equivalent expression levels to LR pair, (3) significant spots of spatial LR co-expression are determined by comparison to the random background, (4) counting of cell type co-occurrence in neighbourhoods of significant LR co-expression, with and without permutation of cell type information, and (5) cell types with significant co-localisation in regions of LR co-expression are predicted as interacting. b stLearn SCTP results for the top-ranked LR pair Gas6-Axl in seqFISH+ data from mouse cortex. c Enlarged panel of the boxed area in b, showing the subventricular zone; black arrows connect interacting cells, and chord plot summarises predicted CCIs facilitated by Gas6-Axl. d Scatter plot highlighting the top predicted LR pair by stLearn SCTP (Gas6-Axl), with the number of significant cells on the y-axis and LR pairs on the x-axis. e Mouse hippocampus Slide-seq data annotated by cluster. f Cells binned by spatial location, with bins representing mixtures of cells similar to Visium data. Bins are represented as pie charts showing the breakdown of cell types. g Significant co-expressing spots for the top-ranked ligand-receptor pair Apoe-Lrp1, illustrating that SCTP can scale to a large number of cells by binning. h Visium ST data from human breast cancer, with each spot coloured by the dominant cell type, as predicted by deconvolution. Red boxes correspond to Ductal Carcinoma In Situ (DCIS), and yellow boxes show regions highlighted in i and j. i, DCIS regions showing significant SCTP predictions for a highly-ranked LR pair (GPC3-IGF1R), overlayed as arrows, where the receiving spot expresses the receptor and the output spot expresses the ligand. j Network diagram of SCTP-predicted CCI results for GPC3-IGF1R. Zoomed-in images of interacting spots (from yellow boxes 1 and 2 in h and i) are shown on the edges, connecting relevant cell types in the graph.

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