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Record W4312210657 · doi:10.1136/jmg-2022-108800

Germline mismatch repair (MMR) gene analyses from English NHS regional molecular genomics laboratories 1996–2020: development of a national resource of patient-level genomics laboratory records

2022· article· en· W4312210657 on OpenAlexaff
Lucy Loong, Catherine Huntley, Fiona E. McRonald, Francesco Santaniello, Joanna Pethick, Bethany Torr, Sophie Allen, Oliver Tulloch, Shilpi Goel, B. A. Shand, Tameera Rahman, Margreet Lüchtenborg, Alice Garrett, Richard Barber, Tina Bedenham, David Bourn, Kirsty Bradshaw, Claire Brooks, Jonathan Bruty, George J. Burghel, Samantha Butler, Chris Buxton, Alison Callaway, Jonathan L A Callaway, James Drummond, Miranda Durkie, Joanne Field, Lucy Jenkins, Terri McVeigh, Roger Mountford, Rodney Nyanhete, Evgenia Petrides, Rachel Robinson, Tracy Scott, Victoria Stinton, James O. Tellez, Andrew J. Wallace, Laura Yarram-Smith, Kate Sahan, Nina Hallowell, Diana Eccles, Paul D.P. Pharoah, Marc Tischkowitz, Antonis C. Antoniou, D. Gareth Evans, Fiona Lalloo, Gail Norbury, Eva Morris, John Burn, Steven Hardy, Clare Turnbull

Bibliographic record

VenueJournal of Medical Genetics · 2022
Typearticle
Languageen
FieldMedicine
TopicGenetic factors in colorectal cancer
Canadian institutionsSt. Thomas HospitalInstitute of Cancer Research
FundersManchester Biomedical Research CentreNational Institute for Health and Care ResearchCancer Research UKBowel Cancer UKNIHR Cambridge Biomedical Research CentreWellcome Trust
KeywordsGenomicsMedicineGeneGeneticsBiologyGenome

Abstract

fetched live from OpenAlex

OBJECTIVE: To describe national patterns of National Health Service (NHS) analysis of mismatch repair (MMR) genes in England using individual-level data submitted to the National Disease Registration Service (NDRS) by the NHS regional molecular genetics laboratories. DESIGN: Laboratories submitted individual-level patient data to NDRS against a prescribed data model, including (1) patient identifiers, (2) test episode data, (3) per-gene results and (4) detected sequence variants. Individualised per-laboratory algorithms were designed and applied in NDRS to extract and map the data to the common data model. Laboratory-level MMR activity audit data from the Clinical Molecular Genetics Society/Association of Clinical Genomic Science were used to assess early years' missing data. RESULTS: Individual-level data from patients undergoing NHS MMR germline genetic testing were submitted from all 13 English laboratories performing MMR analyses, comprising in total 16 722 patients (9649 full-gene, 7073 targeted), with the earliest submission from 2000. The NDRS dataset is estimated to comprise >60% of NHS MMR analyses performed since inception of NHS MMR analysis, with complete national data for full-gene analyses for 2016 onwards. Out of 9649 full-gene tests, 2724 had an abnormal result, approximately 70% of which were (likely) pathogenic. Data linkage to the National Cancer Registry demonstrated colorectal cancer was the most frequent cancer type in which full-gene analysis was performed. CONCLUSION: The NDRS MMR dataset is a unique national pan-laboratory amalgamation of individual-level clinical and genomic patient data with pseudonymised identifiers enabling linkage to other national datasets. This growing resource will enable longitudinal research and can form the basis of a live national genomic disease registry.

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 score0.459
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.036
GPT teacher head0.307
Teacher spread0.271 · 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

Citations12
Published2022
Admission routes1
Has abstractyes

Explore more

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