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Record W2953288458 · doi:10.1038/s41467-018-07905-4

A chemical biology toolbox to study protein methyltransferases and epigenetic signaling

2018· article· en· W2953288458 on OpenAlex
Sebastian Scheer, Suzanne Ackloo, Tiago da Silva Medina, Matthieu Schapira, Fengling Li, Jennifer Ward, Andrew M. Lewis, Jeffrey P. Northrop, Paul L. Richardson, H. Ümit Kanıskan, Yudao Shen, Jing Liu, David Smil, David McLeod, Carlos Zepeda‐Velázquez, Minkui Luo, Jian Jin, Dalia Baršytė-Lovejoy, K. Huber, Daniel D. De Carvalho, Masoud Vedadi, Colby Zaph, Peter J. Brown, 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

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related gene regulation
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health NetworkStructural Genomics ConsortiumOntario Institute for Cancer ResearchUniversity of Toronto
FundersNational Cancer InstituteFundação de Amparo à Pesquisa do Estado de São PauloNational Health and Medical Research CouncilMedical Research CouncilCanadian Institutes of Health ResearchOntario Institute for Cancer ResearchUniversity of North Carolina at Chapel HillCurtin University of TechnologyUniversity of OxfordConselho Nacional de Desenvolvimento Científico e TecnológicoGovernment of OntarioWellcome TrustNovartis PharmaEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentVeskiNational Institute of General Medical SciencesOntario Genomics InstituteEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaACanadian Cancer Society Research InstituteNational Institutes of HealthOntario Ministry of Research, Innovation and ScienceOntario GenomicsGenome CanadaNational Institute of Mental HealthPfizer
KeywordsMethyltransferaseEpigeneticsToolboxComputational biologyChemical biologyBiologyGeneticsMethylationComputer scienceGene

Abstract

fetched live from OpenAlex

Abstract Protein methyltransferases (PMTs) comprise a major class of epigenetic regulatory enzymes with therapeutic relevance. Here we present a collection of chemical probes and associated reagents and data to elucidate the function of human and murine PMTs in cellular studies. Our collection provides inhibitors and antagonists that together modulate most of the key regulatory methylation marks on histones H3 and H4, providing an important resource for modulating cellular epigenomes. We describe a comprehensive and comparative characterization of the probe collection with respect to their potency, selectivity, and mode of inhibition. We demonstrate the utility of this collection in CD4 + T cell differentiation assays revealing the potential of individual probes to alter multiple T cell subpopulations which may have implications for T cell-mediated processes such as inflammation and immuno-oncology. In particular, we demonstrate a role for DOT1L in limiting Th1 cell differentiation and maintaining lineage integrity. This chemical probe collection and associated data form a resource for the study of methylation-mediated signaling in epigenetics, inflammation and beyond.

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)0.000
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 score0.031
Threshold uncertainty score0.463

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0000.000

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 head0.016
GPT teacher head0.322
Teacher spread0.306 · 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