High-throughput behavioral screen in C. elegans reveals Parkinson's disease drug candidates. Author Salman Sohrabi, Danielle Mor, Rachel Kaletsky, William Keyes, Coleen Murphy Publication Year 2021 Type Journal Article Abstract We recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson's disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like 'curling' behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD. Keywords Animals, Caenorhabditis elegans, High-Throughput Screening Assays, Transaminases, Behavior, Animal, Image Interpretation, Computer-Assisted, RNA Interference, Caenorhabditis elegans Proteins, Machine Learning, Neural Networks, Computer, Workflow, Antiparkinson Agents, Drug Repositioning, Posture, Proof of Concept Study Journal Commun Biol Volume 4 Issue 1 Pages 203 Date Published 2021 Feb 15 ISSN Number 2399-3642 DOI 10.1038/s42003-021-01731-z Alternate Journal Commun Biol PMCID PMC7884385 PMID 33589689 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML