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Record W7133016253

Functional Characterization of Proximity-dependent Degraders

2020· dissertation· W7133016253 on OpenAlexaff
Akashdeep Dhillon

Bibliographic record

VenueTSpace · 2020
Typedissertation
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsAmgen (Canada)
Fundersnot available
KeywordsDegronUbiquitinProteasomeUbiquitin-Protein LigasesProtein degradationUbiquitin ligaseIdentification (biology)
DOInot available

Abstract

fetched live from OpenAlex

Over the past two decades, research efforts have aimed to develop event-based therapeutics for targeted protein degradation (TPDs). In recent years, TPDs were developed to hijack E3 ligases for the targeted degradation of proteins of interest. E3 ligases are components of the ubiquitin proteasome system that determine the target specificity of ubiquitylation reactions. The development of novel TPDs is currently limited by a reliance on a few E3 ligases. I established a large-scale forced-proximity screen for identifying potent degraders. I identified UBE2B as a highly potent degrader that outperformed E3 ligases currently recruited by TDPs, suggesting it as a prime candidate for TPD development. Analysis of uncharacterized protein PRR20A suggested wider screen versatility with putative identification of a degron sequence capable of protein degradation both in cis and in trans. Together, my results suggest my novel screening platform can facilitate functional characterization of mammalian quality control and degradation systems and identify novel candidates for TPD development.

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 score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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)0.0020.001

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 head0.019
GPT teacher head0.275
Teacher spread0.256 · 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

Citations0
Published2020
Admission routes1
Has abstractyes

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