Fig. 1

Summary schematic of experimental and analytic pipeline. a One hundred and thirty-five drugs were prioritized for screening based on connectivity with diverse aspects of SZ-related biology. b Cells used for screening comprised seven CCLs (A549, AGS, A673, HEPG2, HT29, MCF7, and VCAP) that were prioritized using LINCs datasets, one additional neural CCL (SH-SY5Y) and hiPSC NPCs from 13 SZ and 13 control individuals (12 each per drug). c Data were generated using the L1000 platform to yield 6650 drug-perturbation transcriptomic profiles (135 drugs tested across 26 hiPSC NPCs and 8 CCLs). After data quality control, normalized expression was converted to d robust Z-scores based on comparison with isogenic DMSO-treated experiments, and used as inputs for e functional molecular enrichments, cell-type-specific (hiPSC NPCs and CCLs) trends, diagnosis-dependent (SZ and control) responses, and chemogenomics analyses. Global transcriptomic responses of two drugs were tested across hiPSC NPCs from three SZ and three control individuals by RNA-seq, as part of a validation of the L1000 results