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Record W4409147590 · doi:10.1002/ajmg.a.64067

Human Phenotype Ontology Annotations for Rare Congenital Conditions: Application to Arthrogryposis Multiplex Congenita

2025· article· en· W4409147590 on OpenAlexafffund
Shahrzad Nematollahi, Reggie C. Hamdy, Harold J. P. van Bosse, Joyce Li, Daniel Blanshay‐Goldberg, Johanna I.P. de Vries, Klaus Dieterich, Isabel Filges, Tanya Bedard, Melissa Haendel, Peter N. Robinson, Noémi Dahan‐Oliel

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsAlberta Children's HospitalMcGill University Health CentreAlberta Health ServicesMcGill UniversityShriners Hospitals for Children - Canada
FundersFonds de Recherche du Québec - SantéNational Human Genome Research InstituteShriners Hospitals for ChildrenAmerican Society for Bone and Mineral Research
KeywordsArthrogryposis multiplex congenitaArthrogryposisPhenotypeOntologyProtocol (science)Encoding (memory)Computer scienceComputational biologyMedicineBiologyGeneticsArtificial intelligencePathologyGene

Abstract

fetched live from OpenAlex

Arthrogryposis multiplex congenita (AMC) represents a large, rare group of congenital conditions. This study addressed major challenges in AMC research posed by the lack of systematic frameworks for data collection and the use of inconsistent terminologies and text descriptions. We aimed to systematically review the Human Phenotype Ontology (HPO) terms, encode AMC phenotypic traits as HPO terms, and pilot test the encoding process in a cohort of children with AMC. An international consensus-based dataset for AMC was used to extract phenotypic traits from the fetal period to adulthood. The encoding process was developed by an international expert panel to expand and revise HPO ontology for joint contractures, as the main characterizing traits in AMC. Using a pre-tested mapping algorithm, the HPO mapping process resulted in a 62% complete match, a 12% incomplete match, and a 26% no match. The encoding process included 37 new terms and annotations and 13 re-structures across 10 different joints. The implemented annotations significantly increased the number of available HPO terms for joint contractures in a cohort of children with AMC (p-value = 0.04). Our encoding and annotation approach may be used as a blueprint for systematic HPO (re)annotations for musculoskeletal and non-musculoskeletal phenotypic traits of AMC.

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)0.005
metaresearch head score (Gemma)0.023
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.014
Threshold uncertainty score0.027

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.023
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0070.005
Science and technology studies0.0010.000
Scholarly communication0.0020.002
Open science0.0010.003
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.001

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 head0.009
GPT teacher head0.325
Teacher spread0.316 · 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 designNot applicable
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

Citations0
Published2025
Admission routes2
Has abstractyes

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