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Record W3118648163 · doi:10.1101/2020.12.30.424747

<i>De novo</i> germline mutation in the Dual Specificity Phosphatase 10 gene accelerates autoimmune diabetes in Non-Obese Diabetic (NOD) mice

2021· preprint· en· W3118648163 on OpenAlexaff
Anne‐Perrine Foray, Sophie Candon, Sara Hildebrand, Cindy Marquet, Fabrice Valette, Coralie Pecquet, Sébastien Lemoine, Francina Langa Vives, Michaël Dumas, Peipei Hu, Pere Santamaría, Stephen Lyon, Lindsay Scott, Chun Hui Bu, Tao Wang, Darui Xu, Eva Marie Y. Moresco, Claudio Scazzocchio, Jean‐François Bach, Bruce Beutler, Lucienne Chatenoud

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Calgary
FundersNational Institutes of HealthInstitut National de la Santé et de la Recherche MédicaleLyda Hill Foundation
KeywordsNodNOD miceBiologyGeneAlleleMutationGermlineSingle-nucleotide polymorphismEndocrinologyGeneticsCancer researchInternal medicineMedicineGenotype

Abstract

fetched live from OpenAlex

Abstract Here we report the isolation by selective breeding of two sublines of Non-Obese Diabetic (NOD) mice exhibiting a significant difference in the incidence of autoimmune type 1 diabetes (T1D). Whole genome sequencing of the NOD/Nck H (high T1D incidence) and NOD/Nck L (low T1D incidence) revealed the presence of a limited number of variants specific to each subline. Treating the age of T1D onset as a quantitative trait and using automated meiotic mapping (AMM), enhanced susceptibility in the NOD/Nck H subline was unambiguously attributed to a recessive allele of Dusp10 which encodes a dual specificity phosphatase. The causative effect of the mutation was verified with a high level of confidence by targeting Dusp10 with CRISPR/Cas9 in NOD/Nck L mice: in these animals a higher incidence of diabetes was observed. Expression of wild-type Dusp10 correlated with higher levels of surface PD-L1 in the islets of NOD/Nck L mice.

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)0.000
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.014
GPT teacher head0.230
Teacher spread0.216 · 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

Citations0
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicPancreatic function and diabetes→French-language works237,207→