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Record W3035964002 · doi:10.1101/2020.06.20.20136184

DNA hypohydroxymethylation in pediatric central nervous system tumors is associated with CTCF binding sites and reduced survival

2020· preprint· en· W3035964002 on OpenAlexaff
Nasim Azizgolshani, Curtis L. Petersen, Youdinghuan Chen, Lucas A. Salas, Laurent Perreard, Lananh Nguyen, Brock C. Christensen

Bibliographic record

VenuemedRxiv · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsUniversity of Toronto
FundersNorris Cotton Cancer CenterNational Institutes of HealthDartmouth College
KeywordsCTCFEpigeneticsBiologyEpigenomeCpG siteDNA binding siteEnhancerDNA methylationCancer researchGliomaEpigenomicsNeuropathologymicroRNATranscription factorGeneGeneticsPathologyGene expressionMedicineDiseasePromoter

Abstract

fetched live from OpenAlex

Abstract Nucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system tumors. We measured genome-scale 5hmC in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using oxidative and bisulfite treatments. Tumor 5hmC localized to regulatory elements crucial to cell identity, including transcription factor binding sites and super-enhancers. A linear model tested the CpG-specific differences in 5hmC between tumor and non-tumor samples, as well as between tumor subtypes. Compared to non-tumor samples, tumors were hypohydroxymethylated across the epigenome. Differentially hydroxymethylated loci among tumor subtypes tended to be hypermethylated and disproportionally found in CTCF binding sites and genes related to posttranscriptional RNA regulation, such as DICER1 . Model-based clustering results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. These results have implications for emerging molecular neuropathology classification approaches and epigenetic therapeutic strategies in childhood brain tumors.

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 score0.006

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 head0.021
GPT teacher head0.243
Teacher spread0.222 · 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

Citations1
Published2020
Admission routes1
Has abstractyes

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