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Record W2557683813 · doi:10.1038/ncomms13555

Increased DNA methylation variability in type 1 diabetes across three immune effector cell types

2016· article· en· W2557683813 on OpenAlexaff
Dirk S. Paul, Andrew E. Teschendorff, Mary Dang, Robert Lowe, Mohammed I. Hawa, Simone Ecker, Huriya Beyan, Stephanie Cunningham, Alexandra Fouts, Anita Ramelius, Frances Burden, Samantha Farrow, Sophia Rowlston, Karola Rehnström, Mattia Frontini, Kate Downes, Stephan Busche, Warren Cheung, Bing Ge, Marie-Michelle Simon, David Bujold, Tony Kwan, Guillaume Bourque, Avik Datta, Ernesto Lowy, Laura Clarke, Paul Flicek, Emanuele Libertini, Simon Heath, Marta Gut, Willem H. Ouwehand, Tomi Pastinen, Nicole Soranzo, Sabine E. Hofer, Beate Karges, Thomas Meißner, Bernhard O. Boehm, Corrado Cilio, Helena Elding Larsson, Åke Lernmark, Andrea K. Steck, Vardhman K. Rakyan, Stephan Beck, Richard David Leslie

Bibliographic record

VenueNature Communications · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDiabetes and associated disorders
Canadian institutionsMcGill UniversityMcGill University and Génome Québec Innovation CentreMcGill Genome Centre
FundersVetenskapsrådetBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftEuropean CommissionNational Institute for Health and Care ResearchMedical Research CouncilEuropean Molecular Biology LaboratoryNIHR Cambridge Biomedical Research CentreBritish Heart FoundationWellcome TrustNHS Blood and Transplant
KeywordsEpigeneticsEpigenomeBiologyDNA methylationEffectorCpG siteImmune systemGeneticsEpigenomicsCell typeMonozygotic twinGeneImmunologyCellGene expression

Abstract

fetched live from OpenAlex

The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially variable CpG positions (DVPs) in T1D twins when compared with their healthy co-twins and when compared with healthy, unrelated individuals. These T1D-associated DVPs are found to be temporally stable and enriched at gene regulatory elements. Integration with cell type-specific gene regulatory circuits highlight pathways involved in immune cell metabolism and the cell cycle, including mTOR signalling. Evidence from cord blood of newborns who progress to overt T1D suggests that the DVPs likely emerge after birth. Our findings, based on 772 methylomes, implicate epigenetic changes that could contribute to disease pathogenesis in T1D.

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)0.001
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 score0.500
Threshold uncertainty score0.350

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 science0.0010.000
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 head0.006
GPT teacher head0.265
Teacher spread0.258 · 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

Citations194
Published2016
Admission routes1
Has abstractyes

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