Extended Data Fig. 10: Cellular neighborhood analysis in IMC data demonstrates the enrichment of CD4+ T cells surrounding HLA-DR+ ductal cells.

a) Bar plot displaying the proportion of HLA-DR+ cytokeratin+ cells from each pancreatic region determined by IMC. b-c) HLA-DR+ cytokeratin+ cells versus percentage of myeloid cells. For each donor group, the median of percentage of each annotated immune subtype and the median HLA-DR+ ductal cell percentage of total cells across all individual donors per donor group was computed. Only myeloid cells demonstrated significant correlation with respect to the number of HLA-DR+ cytokeratin+ cells across donor groups. d) Dendrogram visualization of the clusters of HLA-DR+ cytokeratin+ cells (red), cells neighboring HLA-DR+ cytokeratin+ (blue), and cells distant from HLA-DR+ cytokeratin+ cells (grey) as determined by leveraging the spatial architecture provided by IMC data. e) Boxplots showing the normalized protein expression of different canonical markers in cells neighboring HLA-DR+ cytokeratin+ cells (blue) versus cells neighboring random cells (grey). The number of random cells evaluated was equal to the number of HLA-DR+ cytokeratin+ cells. Differential marker expression significance for neighbors in the IMC analysis was determined using permutation tests. For each marker, the distribution of that marker value for each of the designated n neighbors was compared against 100 distributions derived from n random cells across the entire IMC tree. * indicates p-value < 0.01. Total number of cells in both blue and gray groups is 195,633. Box-and-whisker plots (centre, median; box limits, upper (75th) and lower (25th) percentiles; whiskers, 1.5 × interquartile range; points, outliers). f) CD4⁺ T cells are the number one immune subtypes enriched at the neighborhood of HLA-DR+ cytokeratin+ cells. Annotation of neighbors of HLA-DR+ cytokeratin+ cells was performed our machine-learning based strategy.