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Systems‐Based Analysis of the Pancreatic Cancer‐Specific Glycome Reveals ST6GAL1 as a Driver of Human and Murine Disease

2021· article· en· W3168815929 on OpenAlexafffund
Shuhui Chen, Emma Kurz, Emily Vucic, Gillian Baptiste, Cynthia A. Loomis, Cristina Hajdu, Praveen Agarwal, Dafna Bar Sagi, Lara K. Mahal

Bibliographic record

VenueThe FASEB Journal · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsUniversity of Alberta
FundersNational Cancer InstituteNational Institutes of HealthCanada Excellence Research Chairs, Government of CanadaU.S. Department of Defense
KeywordsGlycomePancreatic cancerGlycanSialic acidCancer researchBiologyPancreasCancerDiseasePathologyMedicineGlycoproteinMolecular biologyBiochemistryGenetics

Abstract

fetched live from OpenAlex

Pancreatic ductal adenocarcinoma (PDA) is the 3 rd leading cause of cancer‐death in the U.S.. Glycans, such as CA‐19‐9, are biomarkers of PDA, but their roles in PDA biology are unclear. Herein, we utilized lectin microarray technology to compare the glycomes of human and murine PDA. We observed common aberrant patterns of glycosylation across both species, including increased levels of α‐2,3‐ and α‐2,6‐sialic acids, bisecting GlcNAc and poly‐LacNAc. Using single cell sequencing and histological data, we identified ST6GAL1, which underlies α‐2,6‐sialic acid, as a potential driver in human PDA. We created a novel mouse in which a pancreas‐specific genetic deletion of ST6GAL1 overlays the well‐established KC mouse model. Analysis of our model showed delayed cancer formation and a significant reduction in fibrosis. Our results highlight the utility of the KC model as an accurate reflection of human disease and identify ST6GAL1 as a key driver of pancreatic cancer initiation and progression.

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)0.000
metaresearch head score (Gemma)0.000
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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.019
GPT teacher head0.295
Teacher spread0.276 · 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

Citations0
Published2021
Admission routes2
Has abstractyes

Explore more

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