Extended Data Fig. 12: CIN is associated with immune suppression in human tumors.

a, Clustered heatmap (average Euclidean distance) showing min-max normalized average log-transformed expression of key pathways and tumor cell CNV Diversity (Methods) used to stratify the 8 human TNBC tumors into CIN^low and CIN^high subsets. b, Violin plots for the significant (p < 0.05) within-sample Spearman correlations between the mean CIN signature and mean Type I IFN (left), non-canonical NF-kB (middle), and hallmark UPR (right) signatures computed using all tumor cells within each sample (n = 10,836 cells from 8 human tumors). Nodes are colored by sample condition (blue: CIN^low, red: CIN^high) and the overlaid box plots denote the minima and maxima (within 1.5*IQR), median, and 1^st and 3^rd quartiles. c, Strip plot showing CIN-dependent differential abundance within human TNBC cohort. Same as Fig. 2b, but for all cell types in the human TNBC cohort. d, Strip plot showing conserved CIN-dependent differential abundance effects (mean enrichment must be both positive or both negative) of cell types in mouse and human TNBC data, ranked by the mean mouse CIN-dependent log₂(fold change) within each cell subtype. Node size is scaled by p-value, so that more significant differential abundance neighborhoods are larger. Bar plots show the mean log₂(fold change) of neighborhoods with significant (p-value <= 0.1) differential abundance scores; if fewer than two significant neighborhoods are detected, all neighborhoods are used in computing the mean. e, ContactTracing circos plot, as in Fig. 4a, intersected with CIN-dependent interactions detected in human TNBC; which are defined as exhibiting CIN-dependent differential expression of the ligand in human tumors (q < 0.05, log₂FC must be in same direction as CIN- and STING- in mouse analysis), and we detection >= 10 CIN-dependent interaction effects in the target cell type. Data provided in Supplementary Table 9. f, Fraction of overlapping CIN-dependent interactions predicted in mouse and human TNBC samples as a function of the top ranked interactions per dataset; evaluated within the subset of interactions that can be mapped between the human and mouse. Each unique interaction (identified by receptor, target cell type, ligand) is ranked by the number of CIN-dependent interaction effects detected in the target cell type, multiplied by the identity function that expression of the ligand is also CIN-dependent in any cell type in the TME.