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Record W3115444894 · doi:10.1371/journal.pgen.1009190

Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density

2020· article· en· W3115444894 on OpenAlexafffund
Anna Swan, Christine Schütt, Jan Rozman, Maria del Mar Muñiz Moreno, Stefan Brandmaier, Michelle Simon, Stefanie Leuchtenberger, Mark Griffiths, Robert Brommage, Piia Keskivali-Bond, Harald Grallert, Thomas Werner, Raffaele Teperino, Lore Becker, Gregor Miller, Ala Moshiri, John R. Seavitt, Derek D. Cissell, Terrence F. Meehan, Elif F. Acar, Christopher J. Lelliott, Ann M. Flenniken, Marie‐France Champy, Tania Sorg, Abdel Ayadi, Robert E. Braun, Heather Cater, Mary E. Dickinson, Paul Flicek, Juan Gallegos, Elena J. Ghirardello, Jason D. Heaney, Sylvie Jacquot, Connor Lally, John G. Logan, Lydia Teboul, Jeremy Mason, Nadine Spielmann, Colin McKerlie, Stephen A. Murray, Lauryl M. J. Nutter, Kristian F. Odfalk, Helen Parkinson, Jan Procházka, Corey Reynolds, Mohammed Selloum, František Špoutil, Karen L. Svenson, Taylor S. Vales, Sara Wells, Jacqueline K. White, Radislav Sedláček, Wolfgang Wurst, K. C. Kent Lloyd, Peter I. Croucher, Helmut Fuchs, Graham R. Williams, J. H. Duncan Bassett, Valérie Gailus‐Durner, Yann Hérault, Ann‐Marie Mallon, Steve D. M. Brown, Philipp Mayer‐Kuckuk, Martin Hrabě de Angelis

Bibliographic record

VenuePLoS Genetics · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBone Metabolism and Diseases
Canadian institutionsSinai Health SystemLunenfeld-Tanenbaum Research InstituteUniversity of ManitobaUniversity of TorontoSickKids FoundationToronto Centre for PhenogenomicsHospital for Sick Children
FundersNational Cancer InstituteNational Eye InstituteCzech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of SciencesMedical Research CouncilPHENOMINAkademie Věd České RepublikyUniversité de StrasbourgInstitut National de la Santé et de la Recherche MédicaleCentre National de la Recherche ScientifiqueMinisterstvo Školství, Mládeže a TělovýchovyCHIST-ERANational Human Genome Research InstituteWellcome TrustAgence Nationale de la RechercheEuropean Regional Development FundEuropean CommissionUniverzita Karlova v PrazeINFRAFRONTIEREuropean Bioinformatics InstituteNational Institutes of HealthOntario GenomicsGenome CanadaWellcome
KeywordsBone mineralBiologyOsteoporosisGeneIn silicoBone remodelingBone densityMutantCandidate geneGeneticsEndocrinology

Abstract

fetched live from OpenAlex

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and 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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.919

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 head0.021
GPT teacher head0.221
Teacher spread0.200 · 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

Citations30
Published2020
Admission routes2
Has abstractyes

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