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bioRxiv · 10.1101/2021.06.07.447456

DRUG-seq Provides Unbiased Biological Activity Readouts for Drug Discovery

Li, J.·Ho, D. J.·Henault, M.·Yang, C.·Neri, M.·Ge, R.·Renner, S.·Mansur, L.·Lindeman, A.·Tumkaya, T.·Russ, C.·Hild, M.·Gubser Keller, C.·Jenkins, J. L.·Worringer, K. A.·Sigoillot, F. D.·Ihry, R. J.
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Abstract

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.

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Li, J., Ho, D. J., Henault, M., Yang, C., Neri, M., Ge, R., Renner, S., Mansur, L., Lindeman, A., Tumkaya, T., Russ, C., Hild, M., Gubser Keller, C., Jenkins, J. L., Worringer, K. A., Sigoillot, F. D., Ihry, R. J.. 2021-06-08. DRUG-seq Provides Unbiased Biological Activity Readouts for Drug Discovery. https://doi.org/10.1101/2021.06.07.447456

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