Extended Data Fig. 7: Fractal dimension and relationships with stromal cells.

a. Distribution of the average minimum Euclidean distance between a stromal cell to its neighboring cancer cell. For every stromal cell in a tumor region slide, the minimum distance to nearest cancer cell was computed. This distance was then averaged for all identified stromal cells in every region to plot the distribution (n = 275 regions; 85 patients). b. Distribution of the fractal dimension of the cancer-stroma cell interface for histology types in the TRACERx cohort (n = 275 regions; 85 patients). c. Box plots to show the difference in fractal dimension between immune hot and cold regions in TRACERx LUAD (n = 113) and LUSC (n = 84). d. Box plots showing the difference in stromal cell percentage between immune hot and cold regions in all (n = 219), LUAD (n = 113), and LUSC (n = 84). e. Scatter plots showing the correlation between fractal dimension and percentage of cells that are stromal or cancer in all tumor regions (n = 275 regions; 85 patients). This shows that fractal dimension was independent of cancer cell composition, with only a weak correlation with stromal cell percentage and no correlation with tumor cellularity. f. Box plots showing the difference in fractal dimension between LUAD tumor regions harboring an LOH event for HLA type A (n = 106), type B (n = 113), type C (n = 108) versus regions that do not, adjusted for multiple comparisons with the corresponding test in Fig. 4c. g. The same test in f repeated for LUSC tumor regions (n = 87) for HLA of any type. h. Box plots showing the difference in tumor-level fractal dimension using the maximum value of regional measures between LUAD tumors (n = 48) harboring a single LOH event for any HLA type, HLA type A, type B and type C versus tumors that do not, independent of predicted clonal neoantigens. Each p-value was generated using a multiple regression linear model and was also adjusted for multiple testing correction. i. The same test in h repeated for LUSC tumors (n = 29) for HLA of any type. For statistical comparisons among groups, a two-sided, non-parametric, unpaired, Wilcoxon signed-rank test was used, unless stated otherwise.