Extended Data Fig. 4: Glandular heterogeneity and multicellular neighborhoods in pancreatic cancer.
a, Ten representative side-by-side comparisons between gland assignments manually annotated by a board-certified pathologist (outlined in red) versus those extracted by the DBSCAN algorithm (outlined in different colors). White arrows highlight differences in gland annotations for six highly concordant example FOVs. b, Distribution of the number of cells across malignant glands. c, Observed (black) and expected (gray) distributions of the interspersion of malignant glands, subset to glands in the top quartile of heterogeneity. d, Log2 fold change (y axis) between the observed and expected summed exponential-transformed distances between CAF subtypes and malignant cells across varying decay radii (x axis) for n = 1000 permutations. e, Left: Depiction of the summed exponential functions (z axis height and color bar, decay radius r = 50 μm) that are generated from CD8 T cells for a representative FOV, with spatial locations of malignant subtypes shown as colored dots. Right: Log2 fold change (y axis) between the observed and expected summed exponential-transformed distances between malignant subtypes and CD8 T cells (using a malignant-centric model) for n = 1000 permutations6. f-g, Log2 fold change between the observed and expected summed exponential-transformed distances between malignant subtypes and CD8 T cells (using a malignant-centric model), for varying decay radii (f) and varying quantile thresholds (g), for n = 1000 permutations. Data for (d-g) are presented as mean values ± 95% confidence interval. Color legends for (f) are shared with (g). Significant results for one-sided permutation (p < 0.001) and two-sided K-S (p < 10−16) tests in panels (c-g) are indicated with square and circle symbols, respectively. Statistical test legends for panels (d-g) are shared with panel (c). h-i, Depiction of the summed exponential functions that are generated from CD8 T cells for varying decay radii r (h) and with spatial locations of shuffled malignant subtype annotations, which serves as the null distribution (i).
