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Record W4206162934 · doi:10.1111/nyas.14745

Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report

2022· article· en· W4206162934 on OpenAlexaff
Jennifer Cable, Eilika Weber‐Ban, Tim Clausen, Kylie J. Walters, Michal Sharon, Daniel Finley, Yangnan Gu, John Hanna, Yue Feng, Sascha Martens, Anne Simonsen, Malene Hansen, Hong Zhang, Jonathan M. Goodwin, Alessio Reggio, Chunmei Chang, Liang Ge, Brenda A. Schulman, Raymond J. Deshaies, Ivan Đikić, J. Wade Harper, Ingrid E. Wertz, Nicolas H. Thomä, Mikołaj Słabicki, Judith Frydman, Ursula Jakob, Della David, Eric J. Bennett, Carolyn R. Bertozzi, Richa Sardana, Vinay V. Eapen, Serena Carra

Bibliographic record

VenueAnnals of the New York Academy of Sciences · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersNational Institute of General Medical SciencesNational Institute on Aging
KeywordsProtein degradationLysosomeCell biologyEndosomeProteasomeUbiquitinAutophagyOrganelleEndoplasmic-reticulum-associated protein degradationFunction (biology)ChemistryDegradation (telecommunications)BiologyComputational biologyBiochemistryComputer scienceEnzyme

Abstract

fetched live from OpenAlex

Targeted protein degradation is critical for proper cellular function and development. Protein degradation pathways, such as the ubiquitin proteasomes system, autophagy, and endosome-lysosome pathway, must be tightly regulated to ensure proper elimination of misfolded and aggregated proteins and regulate changing protein levels during cellular differentiation, while ensuring that normal proteins remain unscathed. Protein degradation pathways have also garnered interest as a means to selectively eliminate target proteins that may be difficult to inhibit via other mechanisms. On June 7 and 8, 2021, several experts in protein degradation pathways met virtually for the Keystone eSymposium "Targeting protein degradation: from small molecules to complex organelles." The event brought together researchers working in different protein degradation pathways in an effort to begin to develop a holistic, integrated vision of protein degradation that incorporates all the major pathways to understand how changes in them can lead to disease pathology and, alternatively, how they can be leveraged for novel therapeutics.

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)0.001
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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.052
Threshold uncertainty score0.381

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.071
GPT teacher head0.306
Teacher spread0.235 · 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

Citations8
Published2022
Admission routes1
Has abstractyes

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