DRUG-seq Provides Unbiased Biological Activity Readouts for Drug Discovery

Unbiased transcriptomic RNA-seq data has provided deep insights about biological processes. However, its impact in drug discovery has been narrow given high costs and low throughput. Proof-of-concept studies with Digital RNA with pertUrbation of Genes (DRUG)-seq demonstrated the potential to address this gap. We extended the DRUG-seq platform by subjecting it to rigorous testing and by adding an open-source analysis pipeline. The results demonstrate high reproducibility and ability to resolve the mechanism(s) of action for a diverse set of compounds. Overall, the protocol and open-source analysis pipeline are a step towards industrializing RNA-seq for high complexity transcriptomics studies performed at a saturating scale.