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Record W2905413732 · doi:10.1101/501239

Non-CG methylation and multiple epigenetic layers associate child abuse with immune and small GTPase dysregulation

2018· preprint· en· W2905413732 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

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsJewish General HospitalCentre Hospitalier Universitaire Sainte-JustineMcGill UniversityDouglas Mental Health University Institute
FundersCanadian Institutes of Health ResearchFondation de FranceFondation pour la Recherche MédicaleFondation Brain CanadaFondation FyssenAmerican Foundation for Suicide Prevention
KeywordsEpigeneticsDNA methylationContext (archaeology)BiologyChromatinHistoneTranscriptomeNeuroscienceSmall GTPasePsychopathologyGeneticsPsychologyGeneGene expressionSignal transductionPsychiatry

Abstract

fetched live from OpenAlex

Abstract 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 described molecular cross-talk among multiple epigenetic mechanisms, including 6 histone marks, DNA methylation and the transcriptome, in subjects with a history of ELA and controls. We first uncovered, in the healthy brain, previously unknown interactions among epigenetic layers, in particular related to non-CG methylation in the CAC context. We then showed 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 indicated that immune-related and small GTPase signaling pathways are most consistently impaired in the amygdala of ELA individuals. Overall, this work provides new insights into epigenetic 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)0.000
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

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)0.0030.000

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 head0.008
GPT teacher head0.204
Teacher spread0.196 · 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

Citations4
Published2018
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicEpigenetics and DNA Methylation→French-language works237,207→