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Record W3089626965 · doi:10.1073/pnas.2007297117

Metabolic precision labeling enables selective probing of O-linked <i>N</i> -acetylgalactosamine glycosylation

2020· article· en· W3089626965 on OpenAlexfundno aff
Marjoke F. Debets, Ömür Y. Tastan, Simon Wisnovsky, Stacy A. Malaker, Nikolaos Angelis, Leonhard Moeckl, Junwon Choi, Helen R. Flynn, Lauren J. S. Wagner, Ganka Bineva‐Todd, Aristotelis Antonopoulos, Anna Cioce, William M. Browne, Zhen Li, David C. Briggs, Holly Douglas, Gaelen T. Hess, Anthony J. Agbay, Chloë Roustan, Svend Kjær, Stuart M. Haslam, Ambrosius P. Snijders, Michael C. Bassik, W. E. Moerner, Vivian Li, Carolyn R. Bertozzi, Benjamin Schumann

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsnot available
FundersNational Institute of General Medical SciencesNational Cancer InstituteStichting voor de Technische WetenschappenEngineering and Physical Sciences Research CouncilCanadian Institutes of Health ResearchNational Institutes of HealthDirectorate for Biological SciencesBiotechnology and Biological Sciences Research CouncilChemistry, Engineering and Medicine for Human Health, Stanford UniversityResearch Councils UKNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustFrancis Crick InstituteCancer Research UKGovernment of CanadaGlaxoSmithKlineMedical Research CouncilHoward Hughes Medical Institute
KeywordsGlycosylationGlycosyltransferaseUridine diphosphateBiochemistryGlycoproteinMutantChemistryTransfectionEnzymeBiologyGene

Abstract

fetched live from OpenAlex

-acetylgalactosamine-4-epimerase (GALE) like conventional GalNAc-based probes. GalNAzMe enters O-GalNAc glycosylation but does not enter other major cell surface glycan types including Asn(N)-linked glycans. We transfect cells with the engineered pyrophosphorylase mut-AGX1 to biosynthesize the nucleotide-sugar donor uridine diphosphate (UDP)-GalNAzMe from a sugar-1-phosphate precursor. Tagged with a bioorthogonal azide group, GalNAzMe serves as an O-glycan-specific reporter in superresolution microscopy, chemical glycoproteomics, a genome-wide CRISPR-knockout (CRISPR-KO) screen, and imaging of intestinal organoids. Additional ectopic expression of an engineered glycosyltransferase, "bump-and-hole" (BH)-GalNAc-T2, boosts labeling in a programmable fashion by increasing incorporation of GalNAzMe into the cell surface glycoproteome. Alleviating the need for GALE-KO cells in metabolic labeling experiments, GalNAzMe is a precision tool that allows a detailed view into the biology of a major type of cancer-relevant protein glycosylation.

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 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)0.001
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 score0.007
Threshold uncertainty score0.245

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.043
GPT teacher head0.310
Teacher spread0.267 · 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 teacher head, 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

Citations90
Published2020
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicGlycosylation and Glycoproteins ResearchFrench-language works237,207