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Record W3110806383 · doi:10.1016/j.isci.2020.101948

Autosomal recessive variants in TUBGCP2 alter the γ-tubulin ring complex leading to neurodevelopmental disease

2020· article· en· W3110806383 on OpenAlexafffund
Serdal Güngör, Yavuz Oktay, Semra Hız, Álvaro Aranguren‐Ibáñez, İpek Polat Kalafatcilar, Ahmet Yaramış, Ezgi Karaca, Uluç Yiş, Ece Sönmezler, Burcu Ekinci, Mahmut Aslan, Elmasnur Yilmaz, Bilge Özgör, B. Sunitha, Nora Szabó, Steven Laurie, Sergi Beltrán, Daniel G. MacArthur, Denisa Hathazi, Ana Töpf, Andreas Roos, Hanns Lochmüller, Isabelle Vernos, Rita Horváth

Bibliographic record

VenueiScience · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrotubule and mitosis dynamics
Canadian institutionsOttawa HospitalChildren's Hospital of Eastern OntarioUniversity of Ottawa
FundersNational Eye InstituteNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteAgència de Gestió d'Ajuts Universitaris i de RecercaAtaxia UKMedical Research CouncilCanadian Institutes of Health ResearchLily FoundationEvelyn TrustBundesministerium für Bildung und ForschungTürkiye Bilimsel ve Teknolojik Araştırma KurumuCanada Research ChairsNational Heart and Lung InstituteAFM-TéléthonMinisterium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-WestfalenTürkiye Bilimler AkademisiCHEO Research InstituteMuscular Dystrophy CanadaBarcelona Institute of Science and TechnologyEuropean Research CouncilMinisterio de Ciencia, Innovación y UniversidadesWellcome TrustFrench Muscular Dystrophy AssociationMuscular Dystrophy AssociationCanada Foundation for InnovationNewton FundBroad Institute
KeywordsDiseaseBiologyRing (chemistry)Neurodevelopmental disorderGeneticsNeuroscienceMedicineChemistryGenePathology

Abstract

fetched live from OpenAlex

encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organization of the cytoskeleton and the extracellular matrix, controlling cellular adhesion and of proteins crucial for neuronal homeostasis including axon guidance. In summary, our functional and proteomic studies link TUBGCP2 and the γ-tubulin complex to the development of the central nervous system in humans.

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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.730
Threshold uncertainty score0.333

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 head0.021
GPT teacher head0.267
Teacher spread0.245 · 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 designBench or experimental
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

Citations16
Published2020
Admission routes2
Has abstractyes

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