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Somatic DNA mutations in the blood of normal and autoimmune individuals.

2008· article· en· W2289814400 on OpenAlexafffund
Tanya R. Da Sylva, Carly S. Gordon, Alison Connor, Edward Keystone, Gillian E. Wu

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEvolution and Genetic Dynamics
Canadian institutionsMount Sinai HospitalWellesley InstituteUniversity Health NetworkUniversity of TorontoYork University
FundersCanadian Institutes of Health Research
KeywordsSomatic cellAutoimmunityAntigenBiologyImmune systemEpitopeMutantGeneMutationImmunologyGenetics

Abstract

fetched live from OpenAlex

We have analyzed blood from normal and autoimmune individuals, finding a previously unrecognized level of somatic DNA mutations. Using a PCR‐cloning technique we have found an average mutational frequency of 10 −3 mutations/bp in two marker genes (a mitochondrial [ND1] and nuclear gene [DLD]). These somatic mutational data from normal and autoimmune individuals suggests a need for re‐evaluation of self tolerance models to incorporate mutated self. Negative selection requires the presentation of self antigens – but what happens when self mutates? Among the possibilities are: a) there may be no B and T cells capable of launching a reaction against the mutated self because no new epitopes were generated by the mutant antigen, b) an immune cell may recognize the mutant antigen as non‐self and react to it but the number of identical mutant antigens may be too small to promote an auto‐immune reaction, or c) the immune cells may bind and react to the mutant antigen and in doing so form a memory response that can cross‐react to the nonmutant self antigen precipitating or supporting autoimmunity. A model of autoimmunity precipitated and/or supported by mutations in self will be presented. Research funded by CIHR.

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)0.000
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

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

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 head0.009
GPT teacher head0.227
Teacher spread0.218 · 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

Citations0
Published2008
Admission routes2
Has abstractyes

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