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Record W3048528205 · doi:10.7554/elife.54572

Building the vertebrate codex using the gene breaking protein trap library

2020· article· en· W3048528205 on OpenAlexafffund
Noriko Ichino, MaKayla R. Serres, Rhianna Urban, Mark D. Urban, Anthony J. Treichel, Kyle Schaefbauer, Lauren Tallant, Gaurav K. Varshney, Kimberly J. Skuster, Melissa S. McNulty, Camden L. Daby, Ying Wáng, Hsin‐Kai Liao, Suzan El‐Rass, Yonghe Ding, Weibin Liu, Jennifer L. Anderson, Mark Wishman, Ankit Sabharwal, Lisa A. Schimmenti, Sridhar Sivasubbu, Darius Balciunas, Matthias Hammerschmidt, Steven Farber, Xiao‐Yan Wen, Xiaolei Xu, Maura McGrail, Jeffrey J. Essner, Shawn M. Burgess, Karl J. Clark, Stephen C. Ekker

Bibliographic record

VenueeLife · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsSt. Michael's Hospital
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesNational Human Genome Research InstituteNational Institute on Drug AbuseNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthCouncil of Scientific and Industrial Research, IndiaMayo Foundation for Medical Education and ResearchRoy J. Carver Charitable Trust
KeywordsVertebrateTrap (plumbing)BiologyGeneComputational biologyGene nomenclatureGeneticsEvolutionary biologyPhysicsZoologyNomenclature

Abstract

fetched live from OpenAlex

One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. Homozygous GBT animals in ryr1b , fras1 , tnnt2a , edar and hmcn1 phenocopied established mutants. 204 cloned lines trapped diverse proteins, including 64 orthologs of human disease-associated genes with 40 as potential new disease models. Severely reduced skeletal muscle Ca 2+ transients in GBT ryr1b homozygous animals validated the ability to explore molecular mechanisms of genetic diseases. This GBT system facilitates novel functional genome annotation towards understanding cellular and molecular underpinnings of vertebrate biology and human disease.

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)0.001
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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0050.005

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 head0.016
GPT teacher head0.279
Teacher spread0.263 · 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 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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