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Systematic Chemogenetic Library Assembly

Canham, Steve and Jenkins, Jeremy and Auld, Douglas (2020) Systematic Chemogenetic Library Assembly. BioRxiv.

Abstract

At the dawn of the 21st century, human genetic sequencing in combination with computationally-enabled data analysis was heralded to streamline the understanding and curing of diseases. Despite great strides in the use of human genetics and large-scale informatics, a long path remains to parlay candidate genes into successful drug candidates. As such, pharmacological modulators, both chemical and biological probes, assembled into chemogenetic libraries continue to be a mainstay of biomedical research and have a tremendous impact in helping to interrogate complex biological systems. Over the course of 6 years, we assembled and grew a dynamic chemogenetic library of chemical probes (a Mechanism-of-Action Box, or MoA Box) using a mixture of data mining and crowdsourcing institutional expertise across a range of cross-functional scientists. While a chemogenetic library is not conceptually unique, we feel that the lessons learned in construction, annotation, application, and sharing of a MoA Box may help spur discussions to advance the field of chemical biology. Additionally, we herein are disclosing, 4518 compounds with primary annotated gene targets; much of our library (~57% of which are commercially available), should readily enable the larger chemical probe community. We hope our efforts will continue to expand through pre-competitive collaboration across biotech, academia, and chemical vendors. Alliances, such as ChemicalProbes.org, will be instrumental in enabling the rapid discovery and enhanced the reproducibility of chemical probes in biomedical research.

Item Type: Article
Date Deposited: 27 May 2020 00:45
Last Modified: 27 May 2020 00:45
URI: https://oak.novartis.com/id/eprint/42506

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