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Record W4403877028 · doi:10.54195/9789493296831

Clinical epigenetics of Mendelian neurodevelopmental disorders

2024· book· en· W4403877028 on OpenAlexfundno aff
Dmitrijs Rots

Bibliographic record

VenueRadboud University Press eBooks · 2024
Typebook
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchManchester Biomedical Research CentreMedical Research CouncilCotton Research and Development CorporationSilicon Valley Community FoundationEuropean CommissionOntario Genomics InstituteDeutsche ForschungsgemeinschaftGovernment of CanadaNational Institute for Health and Care ResearchOntario GenomicsNederlandse Organisatie voor Wetenschappelijk OnderzoekComunidad de MadridGenome CanadaManton Center for Orphan Disease Research, Boston Children's HospitalZonMwSimons Foundation Autism Research InitiativeEesti TeadusagentuurAutism Speaks
KeywordsEpigeneticsMendelian inheritanceNeuroscienceMedicineBiologyGeneticsGene

Abstract

fetched live from OpenAlex

Neurodevelopmental disorders (NDDs) constitute a broad spectrum of rare conditions arising from various genetic and environmental factors. A subset of NDDs are caused by pathogenic variants in a single gene or locus and are termed Mendelian NDDs. These disorders present with diverse symptoms and exhibit significant clinical heterogeneity. In recent years, advancements in genetic technologies and transitioning from phenotype-first to genotype-first approaches have driven a surge in novel gene and Mendelian NDD discoveries, identifying the epigenetic machinery encoding genes as one of the major gene groups associated with Mendelian NDDs. This highlighted that the epigenetic gene regulation is essential for the normal neurodevelopment and can result in Mendelian NDD, when disrupted by a pathogenic genetic variant. Despite technological advancements, interpreting genetic data remains challenging, so a large proportion of the variants are being classified as variants of uncertain significance (VUS). Because of the rarity of these conditions and diagnostic challenges, the true clinical and molecular spectrum of the most Mendelian NDDs largely remain unknown, despite increasing application of the next-generation sequencing. As result, this complicates 1) genetic variant interpretation, as well as 2) diagnosed patient care, requiring further research to characterize these conditions. Therefore, this thesis is aimed to comprehensively characterize the clinical, molecular, and DNA methylation spectrum and features of several Mendelian NDDs, focusing on the disorders of the epigenetic machinery.

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: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: none
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
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
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 head0.017
GPT teacher head0.238
Teacher spread0.221 · 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 designNot applicable
Domainnot available
GenreOther

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

Citations0
Published2024
Admission routes1
Has abstractyes

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