A KNIME-Based Analysis of the Zebrafish Photomotor Response Clusters the Phenotypes of 14 Classes of Neuroactive Molecules

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2016
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Copmans, Daniëlle
van Leeuwen, Matthijs
Ortmann, Julia
de Witte, Peter A. M.
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Journal of Biomolecular Screening. 2016, 21(5), pp. 427-436. ISSN 1087-0571. eISSN 1552-454X. Available under: doi: 10.1177/1087057115618348
Zusammenfassung

Recently, the photomotor response (PMR) of zebrafish embryos was reported as a robust behavior that is useful for high-throughput neuroactive drug discovery and mechanism prediction. Given the complexity of the PMR, there is a need for rapid and easy analysis of the behavioral data. In this study, we developed an automated analysis workflow using the KNIME Analytics Platform and made it freely accessible. This workflow allows us to simultaneously calculate a behavioral fingerprint for all analyzed compounds and to further process the data. Furthermore, to further characterize the potential of PMR for mechanism prediction, we performed PMR analysis of 767 neuroactive compounds covering 14 different receptor classes using the KNIME workflow. We observed a true positive rate of 25% and a false negative rate of 75% in our screening conditions. Among the true positives, all receptor classes were represented, thereby confirming the utility of the PMR assay to identify a broad range of neuroactive molecules. By hierarchical clustering of the behavioral fingerprints, different phenotypical clusters were observed that suggest the utility of PMR for mechanism prediction for adrenergics, dopaminergics, serotonergics, metabotropic glutamatergics, opioids, and ion channel ligands.

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ISO 690COPMANS, Daniëlle, Thorsten MEINL, Christian DIETZ, Matthijs VAN LEEUWEN, Julia ORTMANN, Michael R. BERTHOLD, Peter A. M. DE WITTE, 2016. A KNIME-Based Analysis of the Zebrafish Photomotor Response Clusters the Phenotypes of 14 Classes of Neuroactive Molecules. In: Journal of Biomolecular Screening. 2016, 21(5), pp. 427-436. ISSN 1087-0571. eISSN 1552-454X. Available under: doi: 10.1177/1087057115618348
BibTex
@article{Copmans2016-06-01KNIME-34789,
  year={2016},
  doi={10.1177/1087057115618348},
  title={A KNIME-Based Analysis of the Zebrafish Photomotor Response Clusters the Phenotypes of 14 Classes of Neuroactive Molecules},
  number={5},
  volume={21},
  issn={1087-0571},
  journal={Journal of Biomolecular Screening},
  pages={427--436},
  author={Copmans, Daniëlle and Meinl, Thorsten and Dietz, Christian and van Leeuwen, Matthijs and Ortmann, Julia and Berthold, Michael R. and de Witte, Peter A. M.}
}
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