Fig. 4

A Colocalization heatmaps between fibroblasts and tumor in liver samples 1, 2, and 3. B Using niche-DE marker genes in fibroblasts near tumor as input, pathway enrichment analysis finds ECM organization, collagen formation, and WNT signaling as top processes in fibroblasts in the presence of tumor cells. Spatial heatmaps of CTBP2, COL4A1, and COL1GALT1 confirm expression of pathway-related genes in the presence of tumor. C Spatial heatmap of tumor abundance, fibroblast abundance, and GAL3 expression in CODEX data of liver metastasis of colorectal cancer in patient 4. D Regression of tumor GAL3 expression on their fibroblast effective niche in CODEX data finds a significantly negative coefficient consistent with those found by niche-DE. E Ligand-receptor pairs found between fibroblasts and tumor via niche-LR include LAMA1/ITGA1, JAG2/NOTCH1, and CXCL1/CXCR1. F Clonalscope [41] finds two major tumor subclones in liver sample 1. Analysis finds an amplification of chromosomes 4p and 9q in subclone 2 relative to subclone 1. G Using niche-DE marker genes in fibroblasts near subclone 2 relative to subclone 1 as input, pathway analysis finds translation and glycosylation among enriched processes. Spatial heatmaps of RPS7, NOTCH1, and RPS27A confirm differential expression of pathway-related genes in the region of the tissue containing tumor subclone 2. H Using niche-DE marker genes in fibroblasts near subclone 1 relative to subclone 2 as input, pathway analysis finds interferon signaling, cytokine signaling, and antigen presentation among enriched processes. Spatial heatmaps of IFI6, ISG15, and HLA-F confirm differential expression of pathway-related genes in the region of the tissue containing tumor subclone 1