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Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

2014· article· en· 1,028 citations· W2129867386 on OpenAlex· 10.1016/j.ajhg.2014.03.018

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.
Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

Full frame distilled prediction

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.

Candidate categories
none
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Bench or experimentalConsensus signal: Bench or experimental
Genre
Candidate signal: EmpiricalConsensus signal: Empirical
Teacher disagreement score
0.261
Threshold uncertainty score
0.279
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

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)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.005
GPT teacher head0.201
Teacher spread
0.195 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.

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.

The record

Venue
The American Journal of Human Genetics
Topic
Genomic variations and chromosomal abnormalities
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
SickKids FoundationHolland Bloorview Kids Rehabilitation HospitalMemorial University of NewfoundlandUniversity of AlbertaLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalOntario GenomicsUniversity of TorontoHospital for Sick ChildrenCancer Care OntarioMcMaster UniversityPublic Health Ontario
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentHospital for Sick ChildrenNational Institute of Mental HealthMedical Research CouncilOntario Genomics InstituteWellcome TrustNational Alliance for Research on Schizophrenia and DepressionHealth Research BoardCanadian Institutes of Health ResearchNational Institute of General Medical SciencesNational Institute for Health and Care ResearchGenome CanadaBrain and Behavior Research Foundation
Keywords
Copy-number variationGeneticsAutismGeneBiologyIntellectual disabilitySingle-nucleotide polymorphismAutism spectrum disorderLoss functionPhenotypeMedicineGenomeGenotypePsychiatry
Has abstract in OpenAlex
yes