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Record W4410901524 · doi:10.1136/jmg-2024-110262

Using long-read sequencing to detect and subtype a case with Temple syndrome

2025· article· en· W4410901524 on OpenAlexafffund
Sarah Dada, Vahid Akbari, Duha Hejla, Yaoqing Shen, Katherine Dixon, Sanaa Choufani, Rosanna Weksberg, Cornelius F. Boerkoel, Laura Stewart, Kamilla Schlade‐Bartusiak, Emma Strong, Danya A. Fox, Daniel Gamu, William T. Gibson, Steven J.M. Jones

Bibliographic record

VenueJournal of Medical Genetics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Syndromes and Imprinting
Canadian institutionsUniversity of TorontoBC Children's HospitalUniversity of British ColumbiaHospital for Sick ChildrenB.C. Women's Hospital & Health CentreCanada's Michael Smith Genome Sciences Centre
FundersCanadian Institutes of Health ResearchCanada Research ChairsBC Cancer AgencyBC Children's Hospital
KeywordsGenomic imprintingMethylationDNA methylationUniparental disomyBiologyMultiplexGeneticsImprinting (psychology)Nanopore sequencingComputational biologyEpigenomicsDifferentially methylated regionsDNA sequencingChromosomeGeneKaryotype

Abstract

fetched live from OpenAlex

Temple syndrome is an imprinting disorder resulting from abnormal genomic or epigenomic aberrations of chromosome 14 including maternal uniparental disomy (matUPD), paternal deletion of 14q32, or aberrant methylation of the imprinting control regions at 14q32. Understanding the underlying molecular mechanism is essential to understanding the recurrence risk and physical effects. Currently, diagnosis requires the detection of aberrant methylation and copy number loss via methylation-sensitive assays such as methylation-specific multiplex ligation-dependent probe amplification, and short tandem repeat analysis to detect matUPD and the presence of epimutation. Therefore, a one-step approach that can detect aberrant methylation and underlying genetic mechanisms would be of high clinical value. Here we use nanopore sequencing to delineate the molecular diagnosis of a case with Temple syndrome. We demonstrate the application of nanopore sequencing to detect aberrant methylation and underlying genetic mechanisms simultaneously in this case, thus providing a proof of concept for a one-step approach for molecular diagnosis of this disorder.

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)0.001
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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.687
Threshold uncertainty score0.413

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 science0.0000.000
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 head0.030
GPT teacher head0.314
Teacher spread0.285 · 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.

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

Citations0
Published2025
Admission routes2
Has abstractyes

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