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Record W3157344667 · doi:10.1038/s41467-021-22517-1

Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease

2021· article· en· W3157344667 on OpenAlexafffund
Scott E. Youlten, John P. Kemp, John G. Logan, Elena J. Ghirardello, C. Marcelo Sergio, Michael R.G. Dack, Siobhan E. Guilfoyle, Victoria D. Leitch, Natalie C. Butterfield, Davide Komla‐Ebri, Ryan C. Chai, Alexander P. Corr, James T. Smith, Sindhu T. Mohanty, John Morris, Michelle M. McDonald, Julian M.W. Quinn, Amelia McGlade, Nenad Bartoniček, Matt Jansson, Konstantinos Hatzikotoulas, Melita Irving, Ana Beleza‐Meireles, Fernando Rivadeneira, Emma L. Duncan, J. Brent Richards, David J. Adams, Christopher J. Lelliott, Robert Brink, Tri Giang Phan, John A. Eisman, David M. Evans, Eleftheria Zeggini, Paul A. Baldock, J. H. Duncan Bassett, Graham R. Williams, Peter I. Croucher

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBone Metabolism and Diseases
Canadian institutionsMcGill University
FundersMedical Research CouncilFonds de Recherche du Québec - SantéEuropean CommissionJewish General HospitalNational Institute for Health and Care ResearchAustralian GovernmentNational Institutes of HealthNational Health and Medical Research CouncilHorizon 2020 Framework ProgrammeCancer Research UKUniversity of New South WalesWellcome TrustKing's College LondonErnest Heine Family FoundationCanadian Institutes of Health ResearchWellcome
KeywordsOsteocyteTranscriptomeBiologyGeneCell biologyComputational biologyGeneticsGene expressionOsteoblast

Abstract

fetched live from OpenAlex

Abstract Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders ( P = 2.4 × 10 −22 ) and are associated with the polygenic diseases osteoporosis ( P = 1.8 × 10 −13 ) and osteoarthritis ( P = 1.6 × 10 −7 ). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease.

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)0.000
metaresearch head score (Gemma)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.888
Threshold uncertainty score0.723

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.011
GPT teacher head0.271
Teacher spread0.261 · 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

Citations124
Published2021
Admission routes2
Has abstractyes

Explore more

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