Extended Data Fig. 3: Supplemental analysis for responses to TF perturbation and target prioritization.

a. Scatterplots of logFC of DEGs from DEseq2 Wald test in each class at the sgRNA (X axis) and gene (Y axis) levels. Significant DEGs (BH-adjusted p < 0.05) at the gene level are shown. Red dots denote DEGs detected in ≥2 conditions; Pearson correlation coefficients and two-sided p values are shown; red dashed line represents Y = X. b. Scatterplots of estimated coefficients for differential abundance from DCATS in each class in downsampled (X axis) versus full populations (Y axis); each condition was randomly downsampled to 300, 400 and 600 cells. Pearson correlation coefficients and two-sided p values are shown. Red dashed line represents Y = X. c. Scatterplots showing correlation between summed |estimated coefficient| in cell abundance (X axis) and number of DEGs (Y axis) per cell type within 3 classes (Excitatory Neurons, Inhibitory Neurons, Radial Glia). Pearson correlation coefficients and two-sided p values are shown with regression lines (95% CI). d. Plots showing (left) Euclidean distance to NT, (middle) energy distance⁵⁶ to NT, (right) maximum |log₂FC| of cell abundance at the gene level among eight cell types listed in (e). e. Dotplot showing global changes in cell abundance (color, DCATS coefficient; border, p value) and gene expression (size, number of DEGs, BH-adjusted p < 0.05) across eight cell types. Top row, number of active sgRNAs per TF. f. Dotplot showing global changes in cell abundance and gene expression across three major classes. Note that the overall trend toward depletion of IN_IPCs across perturbations drives broader depletion of the IN lineage at the level of class, even in cases like SOX2, ZNF219 which showed postmitotic IN enrichments.