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Simultaneous analysis of neuroactive compounds in zebrafish

View ORCID ProfileDouglas Myers-Turnbull, View ORCID ProfileJack C Taylor, View ORCID ProfileCole Helsell, Matthew N McCarroll, Chris S Ki, View ORCID ProfileTia A Tummino, Shreya Ravikumar, Reid Kinser, Leo Gendelev, Rebekah Alexander, Michael J Keiser, View ORCID ProfileDavid Kokel
doi: https://doi.org/10.1101/2020.01.01.891432
Douglas Myers-Turnbull
aQuantitative Biosciences Consortium, University of California, San Francisco, CA 94143, USA
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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  • ORCID record for Douglas Myers-Turnbull
Jack C Taylor
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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Cole Helsell
aQuantitative Biosciences Consortium, University of California, San Francisco, CA 94143, USA
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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Matthew N McCarroll
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
cDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
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Chris S Ki
aQuantitative Biosciences Consortium, University of California, San Francisco, CA 94143, USA
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Tia A Tummino
aQuantitative Biosciences Consortium, University of California, San Francisco, CA 94143, USA
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
cDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
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Shreya Ravikumar
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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Reid Kinser
aQuantitative Biosciences Consortium, University of California, San Francisco, CA 94143, USA
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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Leo Gendelev
aQuantitative Biosciences Consortium, University of California, San Francisco, CA 94143, USA
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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Rebekah Alexander
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
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Michael J Keiser
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
cDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
gDepartment of Bioengineering & Therapeutic Sciences, University of California, San Francisco, CA 94143, USA
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David Kokel
bInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA
cDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
hDepartment of Physiology, University of California, San Francisco, CA 94143, USA
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  • For correspondence: dave.kokel@gmail.com
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Abstract

Neuroactive compounds are crucial tools in drug discovery and neuroscience, but it remains difficult to discover neuroactive compounds with new mechanisms of action. To address this need, researchers have developed mid-throughput phenotype-first approaches using zebrafish. This study introduces an open, non-commercial, and extensible hardware/software platform that captures and analyzes drugmodulated phenotypic responses larval zebrafish. We provide full specifications, computer-aided design (CAD) documents, and source code. Accompanying this study, we are also publicly depositing phenotypic data on 3.9 million animals and 34,000 compounds. The data include a high-replicate benchmark set on 14 compounds, a wellcontrolled reference set of 648 known neuroactive compounds, 20 specialized reference sets, a library of 1,520 FDA-approved drugs, 3 screening libraries. This open data resource is curated, structured, tied to extensive metadata, and available under a Creative Commons CC-BY license.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • D.M-T. designed the experiments, performed the analyses, and wrote the paper. D.M-T., C.H., C.S.K., and D.K. developed the hardware and drivers. D.M-T., C.H., and C.S.K. wrote the software. J.C.T. collected the data and assisted design. R.A., T.A.T., and D.M-T. collected preceding data. R.K. compiled the CAD diagrams. S.R. and D.M.-T. trained convolutional neural networks. D.M-T., J.C.T., and L.G. performed the randomization. D.K. and M.J.K. provided financial support and supervision. All authors read and approved the manuscript.

  • The authors declare no competing interest.

  • ↵5 Michael J Keiser. E-mail: keiser{at}keiserlab.org

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Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 15, 2022.
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Simultaneous analysis of neuroactive compounds in zebrafish
Douglas Myers-Turnbull, Jack C Taylor, Cole Helsell, Matthew N McCarroll, Chris S Ki, Tia A Tummino, Shreya Ravikumar, Reid Kinser, Leo Gendelev, Rebekah Alexander, Michael J Keiser, David Kokel
bioRxiv 2020.01.01.891432; doi: https://doi.org/10.1101/2020.01.01.891432
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Simultaneous analysis of neuroactive compounds in zebrafish
Douglas Myers-Turnbull, Jack C Taylor, Cole Helsell, Matthew N McCarroll, Chris S Ki, Tia A Tummino, Shreya Ravikumar, Reid Kinser, Leo Gendelev, Rebekah Alexander, Michael J Keiser, David Kokel
bioRxiv 2020.01.01.891432; doi: https://doi.org/10.1101/2020.01.01.891432

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