Fig. 6 |. Multicellular communities exist in the aging DLPFC brain region.

a, Scheme of the computational framework for estimating multicellular communities: proportions of cell subsets across individuals within each cell type are calculated and combined, and pairwise correlations between all cellular subsets are computed. A multicellular network is derived from the pairwise correlations, associated with AD traits by statistical analysis, and connected components are annotated as cellular communities (Methods). b, A network of cellular subsets reveals coordinated variation across individuals in multiple cell types. Network of coordinated and anti-coordinated cell subsets (nodes). Edges between pairs of subsets with statistically significant correlated proportions across individuals (R > 0.4, two-sided P value threshold = 0.05, solid red line) or anti-correlated (R < −0.4, dashed blue line) based on CelMod proportions (n = 638). snRNA-seq-based network is shown in Extended Data Fig. 7b. Nodes are colored by the cell type and numbered by the subset as in Figs. 2a and 3a,d,h. c, Correlation patterns of proteomic³⁰ expression of signature genes across cell subsets match CelMod estimates. For selected cell subsets, pairwise correlations of snRNA-seq proportions (n = 24, left), CelMod proportions (n = 638, middle) and average protein expression levels of signature genes (n = 400, right). d–f, Cellular communities are linked to AD-associated traits. Cellular network (as in b) of coordinated and anti-coordinated cell subsets (nodes), colored by the associations (multivariable linear regression, FDR 0.01) with AD traits (purple, positive; green, negative association; gray, nonsignificant) for: cognitive decline (d), tangles burden (e) and β-amyloid burden (f). Bottom, each bar represents the connectivity score (no. of positive edges − no. of negative edges)/potential edges between groups of cells according to their association to each trait, showing that cell subsets associated with AD traits are highly connected in the network. Statistical significance for the connectivity score was calculated based on random permutations (one-sided, not adjusted) (Methods): *P = 0.05, **P = 0.01. a, amyloid load; c, cognitive decline; t, tangles load; neg, negatively associated; pos, positively associated; neutral, not associated.