Dataset Information

DRUG-seq Provides Unbiased Biological Activity Readouts for Neuroscience Drug Discovery.

ABSTRACT: Unbiased transcriptomic RNA-seq data has provided deep insights into 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. Furthermore, we demonstrate how this data can be incorporated into a drug discovery project aiming to develop therapeutics for schizophrenia using human stem cell-derived neurons. We identified both an on-target activation signature, induced by a set of chemically distinct positive allosteric modulators of the N-methyl-d-aspartate (NMDA) receptor, and independent off-target effects. Overall, the protocol and open-source analysis pipeline are a step toward industrializing RNA-seq for high-complexity transcriptomics studies performed at a saturating scale.

SUBMITTER: Li J

PROVIDER: S-EPMC9207813 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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DRUG-seq Provides Unbiased Biological Activity Readouts for Neuroscience Drug Discovery.

Li Jingyao J Ho Daniel J DJ Henault Martin M Yang Chian C Neri Marilisa M Ge Robin R Renner Steffen S Mansur Leandra L Lindeman Alicia A Kelly Brian B Tumkaya Tayfun T Ke Xiaoling X Soler-Llavina Gilberto G Shanker Gopi G Russ Carsten C Hild Marc M Gubser Keller Caroline C Jenkins Jeremy L JL Worringer Kathleen A KA Sigoillot Frederic D FD Ihry Robert J RJ

ACS chemical biology 20220504 6

Unbiased transcriptomic RNA-seq data has provided deep insights into 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 ...[more]

PMID: 35508359

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Dataset Information

DRUG-seq Provides Unbiased Biological Activity Readouts for Neuroscience Drug Discovery.

Publications

DRUG-seq Provides Unbiased Biological Activity Readouts for Neuroscience Drug Discovery.

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