Evidence map›Paper›PMID 39551797›Full record

ArticleNature communications2024

Deep phenotypic profiling of neuroactive drugs in larval zebrafish.

Leo Gendelev, Jack Taylor, Douglas Myers-Turnbull, Steven Chen, Matthew N McCarroll, Michelle R Arkin, David Kokel, Michael J Keiser

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  6. Pharmaco-behavioral profiling identifies suppressors of autism gene-associated phenotypes in zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  11. Review
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  14. Behavioral Profiling in Zebrafish Identifies Insecticide-Related Compounds.Journal of agricultural and food chemistry · 2025
    Article
  15. Review
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  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Leo GendelevInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9166-3947
Jack TaylorInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6431-9956
Douglas Myers-TurnbullInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Steven ChenDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Matthew N McCarrollInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
Michelle R ArkinDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9366-6770
David KokelInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA. dave.kokel@gmail.com.
Michael J KeiserInstitute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA. keiser@keiserlab.org.ORCID 0000-0002-1240-2192

Funding

Behavior-based chemical screening for GABAergic and startle modifying drugsR01AA022583 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOKEL, DAVID · 2013 to 2017
$1.6M
NIAAA NIH HHS R01 AA022583Paul G. Allen Family Foundation Allen Distinguished InvestigatorU.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) R01AA022583
6 · The paper itself

Abstract

Behavioral larval zebrafish screens leverage a high-throughput small molecule discovery format to find neuroactive molecules relevant to mammalian physiology. We screen a library of 650 central nervous system active compounds in high replicate to train deep metric learning models on zebrafish behavioral profiles. The machine learning initially exploited subtle artifacts in the phenotypic screen, necessitating a complete experimental re-run with rigorous physical well-wise randomization. These large matched phenotypic screening datasets (initial and well-randomized) provide a unique opportunity to quantify and understand shortcut learning in a full-scale, real-world drug discovery dataset. The final deep metric learning model substantially outperforms correlation distance-the canonical way of computing distances between profiles-and generalizes to an orthogonal dataset of diverse drug-like compounds. We validate predictions by prospective in vitro radio-ligand binding assays against human protein targets, achieving a hit rate of 58% despite crossing species and chemical scaffold boundaries. These neuroactive compounds exhibit diverse chemical scaffolds, demonstrating that zebrafish phenotypic screens combined with metric learning achieve robust scaffold hopping capabilities.

Indexed as

Behavior, AnimalDrug DiscoveryLarvaPhenotypeZebrafishAnimalsCentral Nervous System AgentsDeep LearningDrug Evaluation, PreclinicalHigh-Throughput Screening AssaysHumansSmall Molecule LibrariesCentral Nervous System AgentsSmall Molecule Libraries

Identifiers

PMID39551797
PMCPMC11570628

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.