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CYP2D6 and CYP2C19 Variant Coverage of Commercial Antidepressant Pharmacogenomic Testing Panels Available in Victoria, Australia

2023· preprint· en· W4387020481 on OpenAlexaff
Malcolm Forbes, Malcolm Hopwood, Chad Bousman

Bibliographic record

VenuePreprints.org · 2023
Typepreprint
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsPharmacogenomicsCYP2C19Genetic testingCYP2D6Selection (genetic algorithm)DosingAllelePharmacogeneticsStandardizationMedicineGeneticsBiologyComputer scienceGenotypePharmacologyGeneMachine learning

Abstract

fetched live from OpenAlex

Pharmacogenomic (PGx) testing to inform antidepressant medication selection and dosing is gaining attention from healthcare professionals, patients, and payors in Australia. However, there is often uncertainty regarding which test is most suitable for a particular patient. Here, we identified and evaluated the coverage of CYP2D6 and CYP2C19 variants in commercial antide-pressant PGx testing panels in Victoria, a large and ethnically diverse state of Australia. Test characteristics and star alleles tested for both genes were obtained directly from pathology la-boratories offering PGx testing and compared against the Association of Molecular Pathology’s recommended minimum (Tier 1) and extended (Tier 2) allele sets. Although all tests covered the minimum recommended alleles for CYP2C19, this was not the case for CYP2D6. This study em-phasizes that PGx tests might not be suitable for all individuals in Australia due to the limited range of star alleles assessed. Inadequate haplotype coverage may risk misclassification of an individual’s predicted metabolizer phenotype which has ramifications for depression medica-tion selection and dosage. The study underscores the urgent need for greater standardization in PGx testing and emphasizes the importance of considering genetic ancestry when choosing a PGx testing panel to ensure optimal clinical applicability.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.010
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.160
Threshold uncertainty score0.318

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.010
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.491
GPT teacher head0.484
Teacher spread0.007 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations2
Published2023
Admission routes1
Has abstractyes

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Same venuePreprints.orgSame topicPharmacogenetics and Drug MetabolismFrench-language works237,207