RT Journal Article
SR Electronic
T1 Behavioral fingerprints predict insecticide and anthelmintic mode of action
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.27.428391
DO 10.1101/2021.01.27.428391
A1 Adam McDermott-Rouse
A1 Eleni Minga
A1 Ida Barlow
A1 Luigi Feriani
A1 Philippa H Harlow
A1 Anthony J Flemming
A1 André EX Brown
YR 2021
UL http://biorxiv.org/content/early/2021/01/28/2021.01.27.428391.abstract
AB 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 StatementResearch 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.