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Record W4225808265 · doi:10.1002/trc2.12246

AD Informer Set: Chemical tools to facilitate Alzheimer's disease drug discovery

2022· article· en· W4225808265 on OpenAlexafffund
Frances Potjewyd, Joel K. Annor‐Gyamfi, Jeffrey Aubé, Shaoyou Chu, Ivie L. Conlon, Kevin J. Frankowski, Shiva Krishna Reddy Guduru, Brian Hardy, Megan D. Hopkins, C. Kinoshita, Dmitri Kireev, Emily R. Mason, Charles T. Moerk, Felix Nwogbo, Kenneth H. Pearce, Timothy I. Richardson, David A. Rogers, Disha Soni, Michael A. Stashko, Xiaodong Wang, Carrow I. Wells, Timothy M. Willson, Stephen V. Frye, Jessica E. Young, Alison D. Axtman

Bibliographic record

VenueAlzheimer s & Dementia Translational Research & Clinical Interventions · 2022
Typearticle
Languageen
FieldMedicine
TopicCholinesterase and Neurodegenerative Diseases
Canadian institutionsStructural Genomics Consortium
FundersNational Institute on AgingGenentechNational Institutes of HealthMinistero dello Sviluppo EconomicoGenome CanadaFundação de Amparo à Pesquisa do Estado de São PauloNovartis PharmaCanada Foundation for InnovationOntario Ministry of Economic Development and InnovationWellcome TrustEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaAPfizer
KeywordsSet (abstract data type)Drug discoveryGeneral partnershipComputer scienceDiseaseComputational biologyPortfolioAlzheimer's diseaseDementiaDrug developmentBioinformaticsData scienceMedicineDrugBiologyPharmacologyPathology

Abstract

fetched live from OpenAlex

Introduction: The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP AD) program. Methods: Publicly available resources, such as literature and databases, enabled a data-driven effort to identify existing small molecule modulators for many protein products expressed by the genes nominated by AMP AD and suitable positive control compounds to be included in the set. Compounds contained within the set were manually selected and annotated with associated published, predicted, and/or experimental data. Results: We built an annotated set of 171 small molecule modulators targeting 98 unique proteins that have been nominated by AMP AD consortium members as novel targets for the treatment of AD. The majority of compounds included in the set are inhibitors. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which will require further optimization. A physical copy of the AD Informer Set can be requested on the Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) website. Discussion: Small molecules that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD.

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)0.005
metaresearch head score (Gemma)0.011
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: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.147
Threshold uncertainty score0.491

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.011
Meta-epidemiology (narrow)0.0050.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0100.006
Science and technology studies0.0010.001
Scholarly communication0.0050.003
Open science0.0040.003
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.1470.081

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 head0.514
GPT teacher head0.510
Teacher spread0.004 · 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

Citations5
Published2022
Admission routes2
Has abstractyes

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