Fig. 3: Inter- and intra-patient heterogeneity in CRC tumors and their TME in terms of cell composition and different molecular features.

a–d UMAP embeddings of the gene expression measurements in tumor annotated spots which were colored by different criteria: a per patient, b per the expression of the NUPR1 gene, c per activity of the EGFR pathway and d per activity of the FOXM1 TF. e Cell type proportions in the tumor-surrounding spots per sample as estimated by the results of the deconvolution approach. The number of tumor-surrounding spots for the different samples is also displayed. TA transient amplifiers. f Differential pathway activity computed on pseudo-bulk RNA-seq generated from the tumor-surrounding spots for the different samples. g–j Spatial mapping of the predicted abundance of CMS1, CMS2, CD19⁺CD20⁺ B cells and CD8⁺ T cells overlaid with the pathologist’s tissue annotation in the S3_Col_R sample. k Overlay of the spatial mapping of the clustering at subspot enhanced resolution of the tumor-annotated spots with the pathologist’s tissue annotations in the S5_Rec_Rep1 sample. l Spatial mapping and violin plots per group of the TGFb pathway activity at the enhanced subspot resolution in the S5_Rec_Rep1 sample. A Kruskal–Wallis statistical test was performed to assess whether the pathway activities in the different subclusters originated from the same distribution (p-value).