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Record W4362717907 · doi:10.1038/s41467-023-37377-0

Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer

2023· article· en· W4362717907 on OpenAlexfundno aff
Mary C. Bedard, Tafadzwa Chihanga, A Carlile, Robert Jackson, Marion G. Brusadelli, Denis Lee, Andrew VonHandorf, Mark Rochman, Phillip J. Dexheimer, Jeffrey J. Chalmers, Gerard J. Nuovo, Maria Lehn, David E. Williams, Aditi Kulkarni, Molly Carey, Amanda Jackson, Caroline C. Billingsley, Alice Tang, Chad Zender, Yash Patil, Trisha M. Wise‐Draper, Thomas J. Herzog, Robert L. Ferris, Ady Kendler, Bruce J. Aronow, Matthew Kofron, Marc E. Rothenberg, Matthew T. Weirauch, Koenraad Van Doorslaer, Kathryn A. Wikenheiser‐Brokamp, Paul F. Lambert, Mike Adam, S. Steven Potter, Susanne I. Wells

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicCervical Cancer and HPV Research
Canadian institutionsnot available
FundersNational Institute of Dental and Craniofacial ResearchNational Human Genome Research InstituteUniversity of ArizonaNational Institute of Allergy and Infectious DiseasesNatural Sciences and Engineering Research Council of CanadaCincinnati Children's Hospital Medical CenterUniversity of Arizona Cancer CenterNational Institute of Environmental Health SciencesUniversity of CincinnatiNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsKeratinocyteBiologyCarcinogenesisTranscriptomeEpitheliumCell cycleTranscription factorCancer researchCellCancerCell cultureGeneGene expressionGenetics

Abstract

fetched live from OpenAlex

Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle is dependent on the differentiation program of stratified squamous epithelium, but the landscape of keratinocyte subpopulations which support distinct phases of the viral life cycle has yet to be elucidated. Here, single cell RNA sequencing of HPV16 infected compared to uninfected organoids identifies twelve distinct keratinocyte populations, with a subset mapped to reconstruct their respective 3D geography in stratified squamous epithelium. Instead of conventional terminally differentiated cells, an HPV-reprogrammed keratinocyte subpopulation (HIDDEN cells) forms the surface compartment and requires overexpression of the ELF3/ESE-1 transcription factor. HIDDEN cells are detected throughout stages of human carcinogenesis including primary human cervical intraepithelial neoplasias and HPV positive head and neck cancers, and a possible role in promoting viral carcinogenesis is supported by TCGA analyses. Single cell transcriptome information on HPV-infected versus uninfected epithelium will enable broader studies of the role of individual keratinocyte subpopulations in tumor virus infection and cancer evolution.

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: Observational · Consensus signal: none
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 integrity0.0000.000
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 head0.066
GPT teacher head0.399
Teacher spread0.333 · 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 designObservational
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

Citations30
Published2023
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicCervical Cancer and HPV ResearchFrench-language works237,207