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Record W2787738067 · doi:10.1101/cshperspect.a032995

Therapeutic Opportunities in Eukaryotic Translation

2018· review· en· W2787738067 on OpenAlexafffund
Jennifer Chu, Jerry Pelletier

Bibliographic record

VenueCold Spring Harbor Perspectives in Biology · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsMcGill University
FundersCanadian Institutes of Health Research
KeywordsBiologyTranslation (biology)Small moleculeComputational biologyEukaryotic translationDrug discoveryBioinformaticsGeneticsMessenger RNAGene

Abstract

fetched live from OpenAlex

The ability to block biological processes with selective small molecules provides advantages distinct from most other experimental approaches. These include rapid time to onset, swift reversibility, ability to probe activities in manners that cannot be accessed by genetic means, and the potential to be further developed as therapeutic agents. Small molecule inhibitors can also be used to alter expression and activity without affecting the stoichiometry of interacting partners. These tenets have been especially evident in the field of translation. Small molecule inhibitors were instrumental in enabling investigators to capture short-lived complexes and characterize specific steps of protein synthesis. In addition, several drugs that are the mainstay of modern antimicrobial drug therapy are potent inhibitors of prokaryotic translation. Currently, there is much interest in targeting eukaryotic translation as decades of research have revealed that deregulated protein synthesis in cancer cells represents a targetable vulnerability. In addition to being potential therapeutics, small molecules that manipulate translation have also been shown to influence cognitive processes such as memory. In this review, we focus on small molecule modulators that target the eukaryotic translation initiation apparatus and provide an update on their potential application to the treatment of 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 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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.994
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
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 head0.103
GPT teacher head0.343
Teacher spread0.239 · 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.

Study designNot applicable
Domainnot available
GenreReview

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

Citations39
Published2018
Admission routes2
Has abstractyes

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