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Record W3214657801 · doi:10.1101/2021.11.12.465712

Genomic landscape of drug response reveals novel mediators of anthelmintic resistance

2021· preprint· en· W3214657801 on OpenAlexaff
Stephen R. Doyle, Roz Laing, David J. Bartley, Alison Morrison, Nancy Holroyd, Kirsty Maitland, Alistair Antonopoulos, Umer Chaudhry, Ilona Flis, Sue Howell, Jennifer McIntyre, John S. Gilleard, Andy Tait, Barbara K. Mable, Ray M. Kaplan, Neil Sargison, Collette Britton, Matthew Berriman, Eileen Devaney, James A. Cotton

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldVeterinary
TopicHelminth infection and control
Canadian institutionsUniversity of Calgary
FundersDirectorate for Biological SciencesBiotechnology and Biological Sciences Research CouncilUniversity of GlasgowUK Research and InnovationScottish GovernmentRural and Environment Science and Analytical Services DivisionWellcome Trust
KeywordsIvermectinBiologyDrug resistanceAnthelminticGeneticsAlleleLocus (genetics)LevamisoleGeneResistance (ecology)AbamectinComputational biologyImmunologyEcologyPesticide

Abstract

fetched live from OpenAlex

Abstract Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to improving the efficacy and sustainability of parasite control. Here, we use a genetic cross in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies novel alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor, cky-1 , in ivermectin resistance. This gene is within a locus under selection in ivermectin resistant populations worldwide; functional validation using knockout experiments supports a role for cky-1 overexpression in ivermectin resistance. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode, and identifies variants for the development of molecular diagnostics to combat drug resistance in the field. One-Sentence Summary: Genetic mapping of known and novel anthelmintic resistance-associated alleles in a multi-drug resistant parasitic nematode

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.

How this classification was reachedexpand

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)0.002
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.574
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.001
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 head0.018
GPT teacher head0.249
Teacher spread0.231 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations20
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicHelminth infection and controlFrench-language works237,207