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Record W4390889218 · doi:10.1016/j.ymthe.2024.01.001

Missense suppressor tRNA therapeutics correct disease-causing alleles by misreading the genetic code

2024· article· en· W4390889218 on OpenAlexafffund
Teija M.I. Bily, Ilka U. Heinemann, Patrick O’Donoghue

Bibliographic record

VenueMolecular Therapy · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsWestern University
FundersCanadian Institutes of Health ResearchOntario Ministry of Research and InnovationNatural Sciences and Engineering Research Council of CanadaOntario Ministry of Research, Innovation and ScienceCanada Research Chairs
KeywordsTransfer RNAGenetic codeTranslation (biology)Missense mutationBiologyAminoacylationRibosomeProtein biosynthesisGeneticsAminoacyl tRNA synthetaseT armComputational biologyGeneRNAMutationMessenger RNA

Abstract

fetched live from OpenAlex

In all living cells, transfer RNAs (tRNAs) act as adaptor molecules, linking the nucleic acid sequences of gene products to the accurate production of proteins by the ribosome. Translation fidelity relies on accurate aminoacylation of tRNAs and faithful decoding of each codon through interactions with the anticodon of a cognate aminoacyl-tRNA. Although translation is a high-fidelity process, cells are tolerant to significantly elevated levels of mistakes in protein synthesis. 1 Ruan B. Palioura S. Sabina J. Marvin-Guy L. Kochhar S. Larossa R.A. Söll D. Quality control despite mistranslation caused by an ambiguous genetic code. Proc. Natl. Acad. Sci. USA. 2008; 105: 16502-16507 Crossref PubMed Scopus (96) Google Scholar Engineered mischarged transfer RNAs for correcting pathogenic missense mutationsHou et al.Molecular TherapyDecember 15, 2023In BriefPan and colleagues describe an experimental strategy to engineer mischarged tRNAs and apply such a tRNA to correct a pathogenic missense mutation in a disease-relevant protein and partially restore its function. This work opens the door to applying tRNA therapy in genetic diseases caused by missense mutations. Full-Text PDF

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.018
GPT teacher head0.262
Teacher spread0.244 · 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

Citations6
Published2024
Admission routes2
Has abstractno

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