For single-cell enrichment analyses, publicly available single-cell RNA-seq data were compiled from five studies of the adult human and mouse brain86,109–112. The mean expression for each gene in each cell type was computed from the single-cell expression data (if not provided). For the Zeisel dataset109, we used the mean expression at level 4 (39 cell types from 19 regions for the mouse nervous system). For the Saunders dataset110, we computed the mean expression of the different classes in each of the 9 different brain regions sampled (88 cell types in total). We filtered out any genes with non-unique names, genes not expressed in any cell types, non-protein coding genes, and, for mouse datasets, genes that had no expert curated 1:1 orthologs between mouse and human (Mouse Genome Informatics, The Jackson Laboratory, version 11/22/2016, http://www.informatics.jax.org/downloads/reports/index.html#homology), resulting in 16,472 genes. Gene expression was then scaled to a total of 1 million UMIs (unique molecular identifiers) (or transcript per million (TPM)) for each cell type/tissue. Using a previously described method38, a metric of gene expression specificity was calculated by dividing the expression of
