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Record W3129481113 · doi:10.1038/s41467-021-21365-3

Non-CG methylation and multiple histone profiles associate child abuse with immune and small GTPase dysregulation

2021· article· en· W3129481113 on OpenAlexafffund
Pierre-Éric Lutz, Marc-Aurèle Chay, Alain Pacis, Gary G. Chen, Zahia Aouabed, Elisabetta Maffioletti, Jean‐François Théroux, Jean‐Christophe Grenier, Jennie Yang, Maria L. Aguirre, Carl Ernst, Adriana Redensek, Léon C.L.T. van Kempen, İpek Yalçın, Tony Kwan, Naguib Mechawar, Tomi Pastinen, Gustavo Turecki

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsJewish General HospitalMontreal Heart InstituteCentre Hospitalier Universitaire Sainte-JustineMcGill UniversityDouglas Mental Health University Institute
FundersCanadian Institutes of Health ResearchCIHR Skin Research Training CentreFondation de FranceFondation pour la Recherche MédicaleGovernment of CanadaFondation Brain CanadaFondation FyssenAmerican Foundation for Suicide Prevention
KeywordsEpigeneticsDNA methylationContext (archaeology)HistoneBiologyChromatinTranscriptomeSmall GTPaseEpigenomicsGeneticsNeuroscienceGeneGene expressionSignal transduction

Abstract

fetched live from OpenAlex

Early-life adversity (ELA) is a major predictor of psychopathology, and is thought to increase lifetime risk by epigenetically regulating the genome. Here, focusing on the lateral amygdala, a major brain site for emotional homeostasis, we describe molecular cross-talk among multiple mechanisms of genomic regulation, including 6 histone marks and DNA methylation, and the transcriptome, in subjects with a history of ELA and controls. In the healthy brain tissue, we first uncover interactions between different histone marks and non-CG methylation in the CAC context. Additionally, we find that ELA associates with methylomic changes that are as frequent in the CAC as in the canonical CG context, while these two forms of plasticity occur in sharply distinct genomic regions, features, and chromatin states. Combining these multiple data indicates that immune-related and small GTPase signaling pathways are most consistently impaired in the amygdala of ELA individuals. Overall, this work provides insights into genomic brain regulation as a function of early-life experience.

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 score0.008

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)0.0020.000

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 head0.010
GPT teacher head0.266
Teacher spread0.256 · 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

Citations48
Published2021
Admission routes2
Has abstractyes

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