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Record W2896650065 · doi:10.1101/431544

GRID – Genomics of Rare Immune Disorders: a highly sensitive and specific diagnostic gene panel for patients with primary immunodeficiencies

2018· preprint· en· W2896650065 on OpenAlexaff
Ilenia Simeoni, Olga Shamardina, Sri V. V. Deevi, Moira Thomas, Karyn Mégy, Emily Staples, Deborah Whitehorn, Daniel Duarte, Rutendo Mapeta, Willem H. Ouwehand, Christopher J. Penkett, Paula Rayner-Matthews, Hannah Stark, Jonathan Stephens, Kathleen Stirrups, Ernest Turro, Adrian J. Thrasher, Taco W. Kuijpers, Kenneth G. C. Smith, Sinisa Savic, Siobhan O. Burns, James Thaventhiran, Hana Lango Allen

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsInstitute of Infection and Immunity
FundersMedical Research CouncilGreat Ormond Street Hospital for ChildrenNational Institute for Health and Care ResearchUniversity College LondonWellcome Trust
KeywordsCopy-number variationIndelGeneGenomicsGeneticsPrimary immunodeficiencyImmune systemPhenotypeBiologyGenetic testingMedicineBioinformaticsComputational biologySingle-nucleotide polymorphismGenotypeGenome

Abstract

fetched live from OpenAlex

Abstract Primary Immune disorders affect 15,000 new patients every year in Europe. Genetic tests are usually performed on a single or very limited number of genes leaving the majority of patients without a genetic diagnosis. We designed, optimised and validated a new clinical diagnostic platform called GRID, Genomics of Rare Immune Disorders, to screen in parallel 279 genes, including 2015 IUIS genes, known to be causative of Primary Immune disorders (PID). Validation to clinical standard using more than 58,000 variants in 176 PID patients shows an excellent sensitivity, specificity. The customised and automated bioinformatics pipeline prioritises and reports pertinent Single Nucleotide Variants (SNVs), INsertions and DELetions (INDELs) as well as Copy Number Variants (CNVs). An example of the clinical utility of the GRID panel, is represented by a patient initially diagnosed with X-linked agammaglobulinemia due to a missense variant in the BTK gene with severe inflammatory bowel disease. GRID results identified two additional compound heterozygous variants in IL17RC , potentially driving the altered phenotype.

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)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.008
GPT teacher head0.176
Teacher spread0.168 · 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 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

Citations8
Published2018
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicImmunodeficiency and Autoimmune DisordersFrench-language works237,207