Extended Data Fig. 5: Expression of known MS genesets and deconvoluted cellular composition in WM subgroups.

a) Violin plots of module scores per WM tissue subgroup for genes associated with functional processes altered in MS or subtypes of astrocytic, microglial/macrophage and oligodendrocytic lineage from single cell or single nucleus sequencing studies. Horizontal line depicts median module score. Statistics were performed for subgroup averages, that is, at the sample level. Module scores within active lesion subgroups (n = 4 samples) and act/inact lesion subgroups (n = 6 samples) were compared using repeated measures ANOVA followed by dependent-samples t-test. Module score averages for AIMS, WM-astrocytes and WM inflammatory were not normally distributed and tested using the non-parametric Friedman test followed by a post-hoc Wilcoxon signed-rank test. b) Heatmap depicting the co-occurrence of two different cell types in the same spatial spot. Scale bar indicates the Jaccard index; 1 indicating two cell types always co-occurred, 0 indicating two cell types never co-occurred in spatial spots. Estimated cell type proportions <1% of the total content of the spot were excluded. c) Average estimated percentage of indicated cell types per WM tissue group, CWM and NAWM data presented as samples (circles) and mean (circles), while active and act/inact data presented as mean (circles) ± SD (error bars). Colours refer to deconvoluted cell types. Statistical significance was determined within active lesions (n = 4 samples) and act/inact lesions (n = 6 samples) by repeated measures ANOVA followed by dependent-samples t-test. All statistical tests were two-tailed, and all post-hoc tests were adjusted with Bonferroni’s method. *P < 0.05, **P < 0.01, ***P < 0.001, for exact p-values see Supplementary Table 6. AIMS, astrocytes inflamed in MS; AST, astrocytes; DAM, disease-associated microglia; ex-neuron, excitatory neurons; in-neuron, inhibitory neurons; MG, microglia; MIMS, microglia inflamed in MS; MΦ, macrophages; OLs, oligodendrocytes; OPCs, oligodendrocyte progenitor cells.