Fig. 2: Meta-modules reveal developmental, cortical gene networks.

a, Of the 225 modules, 156 were confidently assigned biological annotations, with most modules associated with synaptic function, immune function, cell division and cell fate. Meta-modules were annotated based on rigorous literature review of meta-module genes and an enrichment analysis of terms from signaling pathway databases (WikiPathway 2021 Human, KEGG 2021 Human and Elsevier Pathway Collection), transcriptional regulatory collections (ChEA 2016, ENCODE and ChEA Consensus TFs from ChIP, TF Perturbations Followed by Expression and TRRUST Transcription Factors 2019) and Gene Ontology sets (GO Biological Process 2021, GO Molecular Function 2021 and GO Cellular Component 2021). b, Meta-modules associated with cell-type-specific functions (that is, that of vascular cells, microglia/immune cells, oligodendrocytes and astrocytes) were active predominantly in those corresponding cell types. Enrichment analysis was calculated by first isolating the cells in the meta-atlas displaying the greatest activity for the indicated module (module-positive cells) and then evaluating proportional enrichment for a given subtype in each module (purple). UMAPs are shown highlighting the distribution of module activity (top UMAP) and cell-type-specific marker gene expression (bottom UMAP) for select meta-modules: module 59 (vascular cells), 4 (microglia), 169 (oligodendrocyte lineage) and 130 (astrocytes). c, Developmental subtypes are represented by multiple modules that show similar levels of subtype specificity and enrichment, as measured by our module specificity score. This metric scores the relative activity of the module in a given cell type as well as the enrichment of a given cell type among module-positive cells. Heat map displaying the module specificity scores for all modules in all developmental subtypes demonstrates that subtypes are overall characterized by several high-scoring modules (blue). Gray arrowheads highlight example vignette modules (from left to right: modules 156, 144, 94, 134, 20 and 189). OPC, oligodendrocyte progenitor cell; pctl, percentile.