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Behavioral fingerprints predict insecticide and anthelmintic mode of action

Adam McDermott-Rouse, View ORCID ProfileEleni Minga, View ORCID ProfileIda Barlow, View ORCID ProfileLuigi Feriani, Philippa H Harlow, Anthony J Flemming, View ORCID ProfileAndré EX Brown
doi: https://doi.org/10.1101/2021.01.27.428391
Adam McDermott-Rouse
1MRC London Institute of Medical Sciences, London, UK
2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
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Eleni Minga
1MRC London Institute of Medical Sciences, London, UK
2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
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  • ORCID record for Eleni Minga
Ida Barlow
1MRC London Institute of Medical Sciences, London, UK
2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
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Luigi Feriani
1MRC London Institute of Medical Sciences, London, UK
2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
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Philippa H Harlow
3Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire, UK
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Anthony J Flemming
3Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire, UK
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André EX Brown
1MRC London Institute of Medical Sciences, London, UK
2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
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  • For correspondence: andre.brown@imperial.ac.uk
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Abstract

Novel invertebrate-killing compounds are required in agriculture and medicine to overcome resistance to existing treatments. Because insecticides and anthelmintics are discovered in phenotypic screens, a crucial step in the discovery process is determining the mode of action of hits. Visible whole-organism symptoms are combined with molecular and physiological data to determine mode of action. However, manual symptomology is laborious and requires symptoms that are strong enough to see by eye. Here we use high-throughput imaging and quantitative phenotyping to measure C. elegans behavioral responses to compounds and train a classifier that predicts mode of action with an accuracy of 88% for a set of ten common modes of action. We also classify compounds within each mode of action to discover pharmacological relationships that are not captured in broad mode of action labels. High-throughput imaging and automated phenotyping could therefore accelerate mode of action discovery in invertebrate-targeting compound development and help to refine mode of action categories.

Competing Interest Statement

Research grant support was provided by the Biotechnology and Biological Sciences Research Council of the UK in partnership with Syngenta UK. AJF and PHH are employees of Syngenta UK. AEXB has consulted for Syngenta UK.

Footnotes

  • andre.brown{at}imperial.ac.uk

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 4.0 International license.
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Posted January 28, 2021.
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Behavioral fingerprints predict insecticide and anthelmintic mode of action
Adam McDermott-Rouse, Eleni Minga, Ida Barlow, Luigi Feriani, Philippa H Harlow, Anthony J Flemming, André EX Brown
bioRxiv 2021.01.27.428391; doi: https://doi.org/10.1101/2021.01.27.428391
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Behavioral fingerprints predict insecticide and anthelmintic mode of action
Adam McDermott-Rouse, Eleni Minga, Ida Barlow, Luigi Feriani, Philippa H Harlow, Anthony J Flemming, André EX Brown
bioRxiv 2021.01.27.428391; doi: https://doi.org/10.1101/2021.01.27.428391

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