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Record W3163660840 · doi:10.1038/s41467-021-22859-w

Single nucleus multi-omics regulatory landscape of the murine pituitary

2021· article· en· W3163660840 on OpenAlexafffund
Frederique Ruf-Zamojski, Zidong Zhang, Michel Zamojski, Gregory R. Smith, Natalia Mendelev, Hanqing Liu, German Nudelman, Mika Moriwaki, Hanna Pinças, Rosa Castanon, Venugopalan D. Nair, Nitish Seenarine, Mary Anne S. Amper, Xiang Zhou, Luisina Ongaro, Chirine Toufaily, Gauthier Schang, Joseph R. Nery, Anna Bartlett, Andrew Aldridge, Nimisha Jain, Gwen V. Childs, Olga G. Troyanskaya, Joseph R. Ecker, Judith L. Turgeon, Corrine K. Welt, Daniel J. Bernard, Stuart C. Sealfon

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsMcGill University
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesCanadian Institutes of Health ResearchUniversity of VirginiaNew York Genome CenterIcahn School of Medicine at Mount SinaiNational Cancer InstituteNational Institutes of HealthGovernment of CanadaU.S. Department of Health and Human ServicesEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentHoward Hughes Medical Institute
KeywordsChromatinBiologyTranscription factorComputational biologyRegulonTranscriptomeDNA methylationTranscriptional regulationGene regulatory networkGeneticsRegulation of gene expressionGeneGene expression

Abstract

fetched live from OpenAlex

To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu.

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 score0.004
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.252
Teacher spread0.233 · 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

Citations77
Published2021
Admission routes2
Has abstractyes

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