MétaCan
Menu
Back to cohort
Record W4396574600 · doi:10.1126/science.adl1624

Risk of meningomyelocele mediated by the common 22q11.2 deletion

2024· article· en· W4396574600 on OpenAlexafffund
Keng Ioi Vong, Sangmoon Lee, Kit Sing Au, T. Blaine Crowley, Valeria Capra, Jeremiah Martino, Meade Haller, Camila Araújo, Hélio Rubens Machado, Renee D. George, Bryn Gerding, Kiely N. James, Valentina Stanley, Nan Jiang, Kameron Alu, Naomi Meave, Anna S. Nidhiry, Fiza Jiwani, Isaac Tang, Ashna Nisal, Ishani Jhamb, Arzoo Patel, Jennifer McEvoy‐Venneri, Chelsea Barrows, Celina Shen, Yoo-Jin Ha, Robyn E. Howarth, Madison Strain, Allison E. Ashley‐Koch, Matloob Azam, Sara Mumtaz, Gyang Markus Bot, Richard H. Finnell, Zoha Kibar, Ahmed I. Marwan, Gia Melikishvili, Hal S. Meltzer, Osvaldo M. Mutchinick, David A. Stevenson, Henry J. Mroczkowski, Betsy Ostrander, Erica Schindewolf, Julie S. Moldenhauer, Elaine H. Zackai, Beverly S. Emanuel, Sixto García‐Miñáur, Beata Nowakowska, Roger E. Stevenson, Maha S. Zaki, Hope Northrup, Hanna K. McNamara, Kimberly A. Aldinger, Ian G. Phelps, Mei Deng, Ian A. Glass, Bernice E. Morrow, Donna M. McDonald‐McGinn, Simone Sanna‐Cherchi, Dolores J. Lamb, Joseph G. Gleeson, Joan T. Le, Philip J. Lupo, Anna Yurrita, José Ramón Medina-Bereciartu, Caroline M. Kolvenbach, Shirlee Shril, Friedhelm Hildebrandt, Mahmoud M. Noureldeen, Aida M. S. Salem, Yukitoshi Takahashi, Hormos Salimi-Dafsari, H. Westley Phillips, Brian W. Hanak, Bülent Kara, Ayfer Sakarya Güneş, David Gonda, Salman Kirmani, Tinatin Tkemaladze

Bibliographic record

VenueScience · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsCentre Hospitalier Universitaire Sainte-Justine
FundersNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteUniversity of WashingtonCanadian Institutes of Health ResearchUniversity of California, IrvineNational Institute of Child Health and Human DevelopmentUniversity of California, San DiegoNational Institute of Diabetes and Digestive and Kidney DiseasesScience and Technology Development FundEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEuropean CommissionBroad InstituteChildren's Hospital of PhiladelphiaNational Institutes of HealthYale University
KeywordsGeneticsBiology

Abstract

fetched live from OpenAlex

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl , one of several neural tube–expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.000
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 head0.009
GPT teacher head0.297
Teacher spread0.288 · 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

Citations21
Published2024
Admission routes2
Has abstractyes

Explore more

Same venueScienceSame topicCongenital heart defects researchFrench-language works237,207