Fig. 5: MESA extends to spatial transcriptomics and augments functional analysis of liver cancer.

a, Visualization of healthy and HCC liver tissue subsamples showing: (1) the cell-type map (top), (2) the diversity heatmap (middle, red: higher diversity, blue: lower diversity) and (3) the map of the diversity hot spots and cold spots (bottom). b, Quantitative assessment of MESA diversity metrics, highlighting significant differences in spatial diversity patterns between healthy (n = 10) and HCC (n = 10) tissue subsamples (same sample size for panels b, c and g). Standard box plot metrics were used throughout. The HCC tissue shows higher values of GDI (P = 0.001) and DPI (P = 0.033), whereas the healthy tissue exhibits higher MDI value (P = 0.007). Statistical comparisons are conducted using two-sided Welch’s t-test. c, Distribution of cell types and cellular cohabitation frequency in healthy and HCC liver tissues. The differences are more pronounced within hot spots versus whole tissue, achieving statistical significance with lower p-values (two-sided Welch’s t-test with BH adjustment). d, Cluster heatmap showing differentially expressed LRI pathways (columns: samples, rows: pathways). Only pathways with differentially expressed LRIs in more than half of the samples are shown. Color intensity represents P values obtained from two-sided permutation tests, adjusted using BH procedure. e, Cells colored by their communication scores (number of detected LRIs), with hot spots marked in light gray. Notably, regions of high communication scores overlap with diversity hot spots. f, The Venn diagram illustrates the number of significant LRIs between tumor-associated macrophages and T cells, identified before and after the integration of the CosMx data with the scRNA-seq data using MaxFuse. Bar plot provides a detailed breakdown of LRIs identified in each subsample, demonstrating an improved analysis spectrum on LRIs with multiomics integration. g, Bubble plot showing detected LR pairs between tumor-associated macrophages and T cells (mean percentage ± 95% confidence interval). Bubble size indicates the number of subsamples in which the corresponding LRI was detected.