Drop-seq profiles from six classes—excitatory neuron (n=82,936 cells), inhibitory neuron (n=7,783), oligodendrocyte/polydendrocyte (n=3,505), microglia/macrophage (n=1,027), astrocyte (n=7,782), and fibroblast-like/endothelial (n=3,578) — were individually extracted from the Frontal and Posterior Cortex DGEs, and run through a single round of the ICA analysis pipeline described above. To calculate the regional skew of ICs (Figure 5A), cells from each region were downsampled to equal representation, and each IC that passed curation was manually thresholded (by examining that IC’s cell score distribution) to identify cells with positive IC scores. The skew was the fraction of supra-threshold frontal cortex cells divided by the total number of positive cells (Skew score is 1 if only FC cells contribute and 0 if only PC cells contribute; Equal contribution is 0.5). Biological ICs were used to generate subclusters within each cell class analysis. Subclusters were classified as having FC versus PC skew if they 1) exhibited >3:1 compositional difference between FC and PC and 2) P < 0.05 (Bonferroni-adjusted) using Barnard’s exact test. To quantify the number of differentially expressed genes between frontal and posterior cortical cells within
