Fig. 2

Global summary of expression trends and frequently perturbed genes in hiPSC NPCs and CCLs. a Multi-dimensional scaling plot of normalized expression data for all drug-induced gene expression profiles across each hiPSC NPC and CCL. Each point represents the normalized gene expression corresponding to a single experiment. b Venn diagrams showing drug perturbation gene differential expression results by comparison type. Drug-gene perturbagen (DGP) comparisons were defined as active (abs-RZS > 2) in one or more of the four within-cell type (CCL, hiPSC NPC, SZ hiPSC NPC, and control hiPSC NPC) comparisons and two between cell-type comparisons (CCL vs. hiPSC NPC, control vs. SZ hiPSC NPC), one row per DGP-comparison combination. Three circles are required, because a particular DGP test may independently be called as active in the CCLs, hiPSC NPCs, and/or CCL vs. hiPSC NPC tests (or control hiPSC NPCs, SZ hiPSC NPCs, and/or control vs. SZ hiPSC NPCs). The first number in each section is the number of drug perturbation gene differential expression counts, whereas the second number shows the number of genes with at least one drug–gene differential expression result. Top panel shows overlap between CCLs, hiPSC NPCs, and CCLs vs. hiPSC NPCs. Bottom panel shows overlap between control hiPSC NPCs, SZ hiPSC NPCs, and control vs. SZ hiPSC NPCs. Twenty-three percent of the 50,744 drug–gene DE had opposite results in hiPSC NPCs and CCLs, but not large enough to meet the DE threshold; 56% had DE results in one cell type but not the other; 20% had effects that were directionally the same in both cell types, but larger in magnitude in one cell type vs. the other; 0.6% had DE results in both cell types but in opposite directions. Twenty-five percent of the 47,510 DE were opposite between SZ and control hiPSC NPCs, but not large enough to meet the DE threshold; 35% represented a DE in one cell type but not the other; 41% represented effects that were directionally the same in both cell types, but larger in magnitude in one cell type than the other; none showed a DE result in opposing directions