a, Dimensionality of publicly available pharmacogenomic
drug screening experiments. The PRISM Repurposing dataset contains approximately
ten-fold more compounds than CTD2 and approximately ten-fold more cell lines
than NCI-60. b, PRISM method overview. Barcoded cell lines are
pooled in groups of 25 and treated with chemical perturbagens. Pools are lysed
5days after perturbation and the relative abundance of mRNA barcodes is measured
using Luminex MagPlex Microspheres to estimate cell viability. c,
Repurposing screen workflow. A primary screen of 4,518 drugs was performed at
2.5 μM, followed by retesting of 1,448 active drugs at 8 doses. Compounds
were annotated as chemotherapy drugs, targeted cancer drugs, or non-oncology
drugs based on approved indications and prior clinical trial disease areas.
d, Drug category representation in the primary and secondary
screens. The secondary screen was enriched for chemotherapies and targeted
cancer therapies.