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Record W2953441293 · doi:10.1093/cercor/bhz115

Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex

2019· article· en· W2953441293 on OpenAlexfundno aff
Annie Vogel Ciernia, Benjamin I. Laufer, Hye‐Yeon Hwang, Keith W. Dunaway, Charles E. Mordaunt, Rochelle L. Coulson, Dag H. Yasui, Janine M. LaSalle

Bibliographic record

VenueCerebral Cortex · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsnot available
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Institute of Mental HealthNational Institute on Alcohol Abuse and AlcoholismNational Institute of Environmental Health SciencesCanadian Institutes of Health ResearchIntellectual and Developmental Disabilities Research CenterBrain and Behavior Research FoundationUniversity of CaliforniaUniversity of California BerkeleyNational Institutes of Health
KeywordsEpigenomicsEpigeneticsDNA methylationBiologyNeurodevelopmental disorderMECP2Differentially methylated regionsNeuroscienceGeneticsRett syndromeGeneGene expressionPhenotype

Abstract

fetched live from OpenAlex

Neurodevelopmental disorders (NDDs) affect 7-14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA cytosine methylation in 49 human cortex samples from 3 different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation changes across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. NDD DMRs were enriched within promoter regions and for transcription factor binding sites with identified methylation sensitivity. DMRs from all 3 disorders were enriched for ontologies related to nervous system development and genes with disrupted expression in brain from neurodevelopmental or neuropsychiatric disorders. Genes associated with NDD DMRs showed expression patterns indicating an important role for altered microglial function during brain development. These findings demonstrate an NDD epigenomic signature in human cortex that will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.284
Threshold uncertainty score0.678

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.007
GPT teacher head0.224
Teacher spread0.217 · 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 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

Citations45
Published2019
Admission routes1
Has abstractyes

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