Fig. 5.

Drug-induced regulation of SZ biology varies between hiPSC NPCs derived from SZ patients compared with healthy controls. a A gene-set enrichment approach was applied to identify drugs that regulated expression of SZ-set genes differently in profiles generated on SZ and control hiPSC NPCs. b Top 30 drugs with highest collective cell-line type-specific perturbation of synaptic protein interaction clique (PPI) communities, genes differentially expressed in prefrontal cortex of individuals with SZ (SZ DE), and genes harboring common and de novo SZ-risk-associated variants. Squares with enrichment FDR > 0.1 are shown as white. Highlighted in bold are the 18/30 drugs that were independently identified as drugs that normalized SZ-related transcriptional signatures in Fig. 3c. c Trimethobenzamide shows strong SZ/control differential regulation of SZ-risk genes (Z-score difference > 1.5 labeled as solid filled circles with dark red, green or blue color). d Haloperidol shows strong SZ/control differential regulation of synaptic PPI communities (representative synaptic PPI communities, Z-score difference > 1.5 labeled as solid filled circles with dark red or blue color). e Strong enrichment observed for drugs that differentially regulated specific synaptic PPI communities (SZ-set drugs), particularly by antipsychotic drugs that targeted dopaminergic and serotoninergic neurotransmitter receptors (chemogenomic features)