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Record W2903452493 · doi:10.1101/484394

Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution

2018· preprint· en· W2903452493 on OpenAlexfundno aff
Grant Duclos, Vitor H. Teixeira, Patrick Autissier, Yaron Gesthalter, Marjan Reinders-Luinge, Robert Terrano, Yves M. Dumas, Gang Liu, Sarah A. Mazzilli, Corry‐Anke Brandsma, Maarten van den Berge, Sam M. Janes, Wim Timens, Marc E. Lenburg, Avrum Spira, Joshua D. Campbell, Jennifer Beane

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldMedicine
TopicNeonatal Respiratory Health Research
Canadian institutionsnot available
FundersUniversity of California, Los AngelesNational Institutes of HealthRoy Castle Lung Cancer FoundationU.S. Department of DefenseUniversity College London Hospitals NHS Foundation TrustRosetrees TrustSchool of Medicine, New York UniversityNational Institute for Health and Care ResearchUCL Hospitals Charitable FoundationSchool of Medicine, Boston UniversityYork UniversityWellcome TrustLUNGevity Foundation
KeywordsEpitheliumBiologyRespiratory epitheliumCellLungCell typePathologyHyperplasiaGoblet cellBronchusCell biologyMedicineRespiratory diseaseGeneticsInternal medicine

Abstract

fetched live from OpenAlex

ABSTRACT The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to perform functions, such as mucociliary clearance, that defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, the precise effects of this exposure on specific cell types are not well-understood. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses identified thirteen cell clusters defined by unique combinations of nineteen distinct gene sets. Expression of a set of toxin metabolism genes localized to ciliated cells from smokers. Smoking-induced airway remodeling was characterized by a loss of club cells and extensive goblet cell hyperplasia. Finally, we identified a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular and molecular alterations in the human bronchial epithelium that may contribute to the onset of smoking-associated lung diseases.

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 score0.002

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 head0.070
GPT teacher head0.309
Teacher spread0.239 · 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

Citations10
Published2018
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicNeonatal Respiratory Health ResearchFrench-language works237,207