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Record W4302424591 · doi:10.1038/s41467-022-33511-6

The immune factors driving DNA methylation variation in human blood

2022· article· en· W4302424591 on OpenAlexaff
Jacob Bergstedt, Sadoune Ait Kaci Azzou, Kristin Tsuo, Anthony Jaquaniello, Alejandra Urrutia, Maxime Rotival, David Lin, Julia L. MacIsaac, Michael S. Kobor, Matthew L. Albert, Darragh Duffy, Étienne Patin, Lluís Quintana‐Murci, Laurent Abel, Andrés Alcover, Hugues Aschard, Philippe Bousso, Nollaig M. Bourke, Petter Brodin, Pierre Bruhns, Nadine Cerf–Bensussan, Ana Cumano, Christophe d’Enfert, Ludovic Deriano, Marie‐Agnès Dillies, James P. Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Milena Hasan, Gunilla Karlsson Hedestam, Serge Herçberg, Molly A. Ingersoll, Olivier Lantz, Rose Anne Kenny, Mickaël Ménager, Frédérique Michel, Hugo Mouquet, Cliona O’Farrelly, Sandra Pellegrini, Antonio Rausell, Frédéric Rieux‐Laucat, Lars Rogge, Magnus Fontes, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie‐Noëlle Ungeheuer, Christophe Zimmer

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsUniversity of British Columbia
FundersAgence Nationale de la RechercheDartmouth College
KeywordsDNA methylationImmune systemDNAVariation (astronomy)MethylationComputational biologyBiologyGeneticsGeneGene expressionPhysics

Abstract

fetched live from OpenAlex

Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping. We show that DNA methylation differs substantially between naïve and memory T cells, supporting the need for adjustment on these cell-types. By doing so, we find that latent cytomegalovirus infection drives DNA methylation variation and provide further support that the increased dispersion of DNA methylation with aging is due to epigenetic drift. Finally, our results indicate that cellular composition and DNA sequence variation are the strongest predictors of DNA methylation, highlighting critical factors for medical epigenomics studies.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 science0.0000.000
Research integrity0.0000.000
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 head0.014
GPT teacher head0.294
Teacher spread0.280 · 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

Citations78
Published2022
Admission routes1
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicEpigenetics and DNA MethylationFrench-language works237,207