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Record W19422881 · doi:10.1101/gr.192005.115

Bacterial infection remodels the DNA methylation landscape of human dendritic cells

2015· article· en· W19422881 on OpenAlexafffund
Alain Pacis, Ludovic Tailleux, Alexander M. Morin, John Lambourne, Julia L. MacIsaac, Vania Yotova, Anne Dumaine, Anne Danckaert, Francesca Luca, Jean‐Christophe Grenier, Kasper D. Hansen, Brigitte Gicquel, Miao Yu, Athma A. Pai, Chuan He, Jenny Tung, Tomi Pastinen, Michael S. Kobor, Roger Piqué-Regi, Yoav Gilad, Luis B. Barreiro

Bibliographic record

VenueGenome Research · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsMcGill UniversityMcGill University and Génome Québec Innovation CentreUniversity of British ColumbiaChild and Family Research InstituteUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersNational Institute of Allergy and Infectious DiseasesNational Human Genome Research InstituteCanadian Institutes of Health ResearchNational Institutes of HealthCompute CanadaCanada Research ChairsCanadian Institute for Advanced Research
KeywordsBiologyDNA demethylationDNA methylationEpigeneticsChromatinHistoneEpigenomicsEpigenetics of physical exerciseEnhancerDNACell biologyMethylationRegulation of gene expressionGeneticsDemethylationTranscription (linguistics)GeneGene expression

Abstract

fetched live from OpenAlex

DNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells (DCs) with a live pathogenic bacteria is associated with rapid and active demethylation at thousands of loci, independent of cell division. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced demethylation rarely occurs at promoter regions and instead localizes to distal enhancer elements, including those that regulate the activation of key immune transcription factors. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and increased chromatin accessibility, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response to infection, even in nonproliferating cells.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

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 integrity0.0000.000
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 head0.088
GPT teacher head0.367
Teacher spread0.278 · 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

Citations240
Published2015
Admission routes2
Has abstractyes

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