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International Union of Basic and Clinical Pharmacology. Guidelines for GPCR ligand bias

2021· preprint· en· W4243910563 on OpenAlexaff
Peter Kolb, Terry Kenakin, S P H Alexander, Marcel Bermúdez, Laura Bohn, Christian S. Breinholt, Michel Bouvier, Frederick J. Ehlert, Stephen J. Hill, Kirill A. Martemyanov, Richard D Neubig, H. Ongun Onaran, Sudar Rajagopal, Bryan L. Roth, Jana Selent, Arun K. Shukla, M. Sommer, David E. Gloriam

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsTerminologyG protein-coupled receptorFunctional selectivityReceptorDrug discoverySignal transductionLigand (biochemistry)Computational biologyNeurosciencePharmacologyBiologyData scienceBioinformaticsComputer scienceCell biologyBiochemistry

Abstract

fetched live from OpenAlex

G protein-coupled receptors modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Notably, depending on which ligand has activated a particular receptor, it can engage different intracellular transducers. This paradigm of ligand-dependent ‘biased signaling’ dictates a need to advance beyond the level of receptors to consider the combined ligand-receptor pair in order to understand physiological signaling. Bias signaling also has the potential to improve medicines by reducing adverse effects. However, this is challenged by inconsistent interpretation of results and lack of commonly agreed guidelines. Here, we present recommended terminology and guidelines to conduct, report and quantify bias in a comparable and reproducible fashion. We expect these recommendations will facilitate a common understanding of experiments and findings across basic receptor research and drug discovery, while the area and the analytical methods to measure bias are still evolving, especially in complex cellular, tissue and organismal systems.

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)0.042
metaresearch head score (Gemma)0.072
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.042
Threshold uncertainty score0.224

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0420.072
Meta-epidemiology (narrow)0.0010.002
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0050.007
Science and technology studies0.0020.003
Scholarly communication0.0060.004
Open science0.0070.004
Research integrity0.0120.018
Insufficient payload (model declined to judge)0.0340.056

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 head0.122
GPT teacher head0.414
Teacher spread0.293 · 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 designNot applicable
Domainnot available
GenreMethods

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

Citations1
Published2021
Admission routes1
Has abstractyes

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