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Record W4206515520 · doi:10.1039/d1md00228g

Target 2035 – update on the quest for a probe for every protein

2021· editorial· en· W4206515520 on OpenAlex
Susanne Müller, Suzanne Ackloo, Arij Al Chawaf, Bissan Al‐Lazikani, Albert A. Antolín, Jonathan B. Baell, Hartmut Beck, Shaunna Beedie, Ulrich A. K. Betz, G.A. Bezerra, Paul E. Brennan, David A. Brown, Peter J. Brown, Alex N. Bullock, Adrian J. Carter, A. Chaikuad, Mathilde Chaineau, Alessio Ciulli, Ian Collins, Jan Dreher, David H. Drewry, Kristina Edfeldt, A.M. Edwards, Ursula Egner, Stephen V. Frye, Stephen M. Fuchs, Matthew D. Hall, Ingo V. Hartung, Alexander Hillisch, Stephen Hitchcock, Evert Homan, Natarajan Kannan, James R. Kiefer, Stefan Knapp, Milka Kostić, Stefan Kubicek, Andrew R. Leach, S. Lindemann, Brian D. Marsden, Hisanori Matsui, Jordan L. Meier, Daniel Merk, Maurice Michel, Maxwell R. Morgan, Anke Mueller‐Fahrnow, Dafydd R. Owen, Benjamin Perry, Saul H. Rosenberg, Kumar Singh Saikatendu, Matthieu Schapira, Cora Scholten, Sujata Sharma, Anton Simeonov, M. Sundström, Giulio Superti‐Furga, Matthew H. Todd, Claudia Tredup, Masoud Vedadi, F. von Delft, Timothy M. Willson, Georg E. Winter, Paul Workman, C.H. Arrowsmith

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueRSC Medicinal Chemistry · 2021
Typeeditorial
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsMcGill UniversityPrincess Margaret Cancer CentreMontreal Neurological Institute and HospitalStructural Genomics ConsortiumUniversity of Toronto
FundersGenentechGeneralitat de CatalunyaNational Institute for Health and Care ResearchCancer Research UKOntario Genomics InstituteMark Foundation For Cancer ResearchWellcome TrustMcGill UniversityRoyal Marsden NHS Foundation TrustPfizerEuropean CommissionChordoma FoundationOntario GenomicsGenome CanadaNational Cancer InstituteSeventh Framework ProgrammeEuropean Federation of Pharmaceutical Industries and AssociationsAgència per a la Competitivitat de l’EmpresaEuropean Molecular Biology LaboratoryMerck KGaAInnovative Medicines InitiativeWellcome
KeywordsHuman proteome projectProteomeHuman genomeComputational biologyHuman proteinsBiologyGenomeProteomicsBioinformaticsGeneticsGene

Abstract

fetched live from OpenAlex

Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. The challenge of translating the wealth of new knowledge from genomics into new medicines is that proteins, and not genes, are the primary executers of biological function. Therefore, much of how biology works in health and disease must be understood through the lens of protein function. Accordingly, a subset of human proteins has been at the heart of research interests of scientists over the centuries, and we have accumulated varying degrees of knowledge about approximately 65% of the human proteome. Nevertheless, a large proportion of proteins in the human proteome (∼35%) remains uncharacterized, and less than 5% of the human proteome has been successfully targeted for drug discovery. This highlights the profound disconnect between our abilities to obtain genetic information and subsequent development of effective medicines. Target 2035 is an international federation of biomedical scientists from the public and private sectors, which aims to address this gap by developing and applying new technologies to create by year 2035 chemogenomic libraries, chemical probes, and/or biological probes for the entire human proteome.

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.

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)0.004
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: Not applicable
GenreCandidate signal: Editorial · Consensus signal: Editorial
Teacher disagreement score0.190
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
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 science0.0010.000
Research integrity0.0010.001
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 head0.009
GPT teacher head0.258
Teacher spread0.250 · 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