Behavioral fingerprints predict insecticide and anthelmintic mode of action.
Mol Syst Biol
; 17(5): e10267, 2021 05.
Article
de En
| MEDLINE
| ID: mdl-34031985
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 Caenorhabditis 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 substructure that is 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Caenorhabditis elegans
/
Biologie des systèmes
/
Insecticides
/
Anthelminthiques
Type d'étude:
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Animals
Langue:
En
Journal:
Mol Syst Biol
Sujet du journal:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
Royaume-Uni