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Record W1156765303 · doi:10.1038/ncomms8485

Caenorhabditis elegans is a useful model for anthelmintic discovery

2015· article· en· W1156765303 on OpenAlex
Andrew R. Burns, Genna M. Luciani, Gabriel Musso, Rachel Bagg, May Yeo, Yuqian Zhang, Luckshi Rajendran, John Glavin, Robert P. Hunter, Elizabeth Redman, Susan Stasiuk, Michael R Schertzberg, G. Angus McQuibban, Conor R. Caffrey, Sean R. Cutler, Mike Tyers, Guri Giaever, Corey Nislow, Calum A. MacRae, John S. Gilleard, Peter J. Roy

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics, Aging, and Longevity in Model Organisms
Canadian institutionsUniversity of British ColumbiaInstitute for Research in Immunology and CancerCanada Research ChairsUniversité de MontréalUniversity of CalgaryUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchUniversity of TorontoNational Institute of Neurological Disorders and StrokeHarvard Stem Cell InstituteNational Institutes of HealthNational Heart, Lung, and Blood InstituteUniversity of Calgary
KeywordsCaenorhabditis elegansAnthelminticBiologyNematodeZebrafishDrug discoveryModel organismPopulationComputational biologyResistance (ecology)EffectorGeneticsBioinformaticsCell biologyGeneEcologyMedicine

Abstract

fetched live from OpenAlex

Parasitic nematodes infect one quarter of the world's population and impact all humans through widespread infection of crops and livestock. Resistance to current anthelmintics has prompted the search for new drugs. Traditional screens that rely on parasitic worms are costly and labour intensive and target-based approaches have failed to yield novel anthelmintics. Here, we present our screen of 67,012 compounds to identify those that kill the non-parasitic nematode Caenorhabditis elegans. We then rescreen our hits in two parasitic nematode species and two vertebrate models (HEK293 cells and zebrafish), and identify 30 structurally distinct anthelmintic lead molecules. Genetic screens of 19 million C. elegans mutants reveal those nematicides for which the generation of resistance is and is not likely. We identify the target of one lead with nematode specificity and nanomolar potency as complex II of the electron transport chain. This work establishes C. elegans as an effective and cost-efficient model system for anthelmintic discovery.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.392
Threshold uncertainty score0.646

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.038
GPT teacher head0.306
Teacher spread0.268 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it