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Record W2761793335 · doi:10.1038/s41467-017-00595-4

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

2017· article· en· W2761793335 on OpenAlexafffund
Michael R. Bowl, Michelle M. Simon, Neil J. Ingham, Simon Greenaway, Luís Santos, Heather Cater, Sarah E. Taylor, Jeremy Mason, Natalja Kurbatova, Selina Pearson, Lynette Bower, Dave Clary, Hamid Méziane, Patrick T. Reilly, Osamu Minowa, Lois Kelsey, Sue Allen, Sharon Clementson-Mobbs, Gemma Codner, Martin Fray, Wendy Gardiner, Russell Joynson, Janet Kenyon, Jorik Loeffler, Barbara Nell, Andrew Parker, Deen Quwailid, Michelle Stewart, Alison Walling, Rumana Zaman, Chao-Kung Chen, Nathalie Conte, Peter Matthews, Mike Relac, Ilinca Tudose, Jonathan Warren, Elise Le Marchand, Amal El Amri, Leila El Fertak, Hamid Ennah, Dalila Ali-Hadji, Abdel Ayadi, Marie Wattenhofer‐Donzé, David Moulaert, Sylvie Jacquot, Philippe André, Marie‐Christine Birling, Guillaume Pavlovic, Valérie Lalanne, Aline Lux, Fabrice Riet, Christophe Mittelhaeuser, Raphaël Bour, Alain Guimond, Chaouki Bam’Hamed, Sophie Leblanc, Laurent Vasseur, Mohammed Selloum, Tania Sorg, Shinya Ayabe, Tamio Furuse, Hideki Kaneda, Kimio Kobayashi, Hiroshi Masuya, Ikuo Miura, Yuichi Obata, Tomohiro Suzuki, Masaru Tamura, Nobuhiko Tanaka, Ikuko Yamada, Atsushi Yoshiki, Zorana Berberovic, Mohammed Bubshait, Jorge Cabezas, Tracy Carroll, Greg Clark, Shannon Clarke, Amie Creighton, Ozge Danisment, Mohammad Eskandarian, Patricia Feugas, Marina Gertsenstein, Ruolin Guo, Jane Hunter, Elsa Jacob, Qing Lan, Valerie Laurin, Napoleon Law, Sue MacMaster, D. Craig Miller, Lily Morikawa, Susan Newbigging, Celeste Owen, Patricia Penton, Monica Pereira, Dawei Qu, Xueyuan Shang, Gillian Sleep, Khondoker Sohel, Sandra Tondat, Yanchun Wang, Igor Vukobradovic, Yingchun Zhu, Francesco Chiani, Chiara Di Pietro, Gianfranco Di Segni, Olga Ermakova, Filomena Ferrara, Paolo Fruscoloni, Alessia Gambadoro, Serena Gastaldi, Elisabetta Golini, Gina La Sala, Silvia Mandillo, Daniela Marazziti, Marzia Massimi, Rafaele Matteoni, Tiziana Orsini, Miriam Pasquini, Marcello Raspa, Aline Rauch, Gianfranco Rossi, Nicoletta Rossi, Sabrina Putti, Ferdinando Scavizzi, Giuseppe D. Tocchini-Valentini, Joachim Beig, Antje Bürger, Florian Giesert, Jochen Graw, Ralf Kühn, Oskar Oritz, Joel Schick, Claudia Seisenberger, Oana V. Amarie, Lillian Garrett, Sabine M. Hölter, Annemarie Zimprich, Juan Antonio Aguilar‐Pimentel, Johannes Beckers, Robert Brommage, Julia Calzada‐Wack, Helmut Fuchs, Valérie Gailus‐Durner, Christoph Lengger, Stefanie Leuchtenberger, Holger Maier, Susan Marschall, Kristin Moreth, Frauke Neff, Manuela A. Östereicher, Jan Rozman, Ralph Steinkamp, Claudia Stoeger, Irina Treise, Tobias Stoeger, Ali Önder Yildrim, Oliver Eickelberg, Lore Becker, Thomas Klopstock, Markus Ollert, Dirk H. Busch, Carsten B. Schmidt‐Weber, Raffi Bekeredjian, Andreas Zimmer, Birgit Rathkolb, Eckhard Wolf, Martin Klingenspor, Glauco P. Tocchini‐Valentini, Xiang Gao, Allan Bradley, William C. Skarnes, Mark D. Moore, Arthur L. Beaudet, Monica J. Justice, John Seavitt, Mary E. Dickinson, Wolfgang Wurst, Martin Hrabě de Angelis, Yann Hérault, Shigeharu Wakana, Lauryl M. J. Nutter, Ann M. Flenniken, Colin McKerlie, Stephen A. Murray, Karen L. Svenson, David B. West, K. C. Kent Lloyd, David J. Adams, Jacqui White, Natasha A. Karp, Paul Flicek, Damian Smedley, Terrence F. Meehan, Helen Parkinson, Lydia Teboul, Sara Wells, Karen P. Steel, Ann‐Marie Mallon, Steve D. M. Brown

Bibliographic record

VenueNature Communications · 2017
Typearticle
Languageen
FieldNeuroscience
TopicHearing, Cochlea, Tinnitus, Genetics
Canadian institutionsToronto Centre for PhenogenomicsHospital for Sick ChildrenMount Sinai Hospital
FundersBiotechnology and Biological Sciences Research CouncilMedical Research CouncilCentre National de la Recherche ScientifiqueInstitut National de la Santé et de la Recherche MédicaleNational Human Genome Research InstituteWellcome TrustAgence Nationale de la RechercheGovernment of CanadaPHENOMINEuropean CommissionGenome CanadaOntario GenomicsNational Institutes of Health
KeywordsHearing lossCandidate geneBiologyLoss functionGeneticsGeneAuditory systemGenetic screenGenetic heterogeneityPhenotypeAudiologyMedicineNeuroscience

Abstract

fetched live from OpenAlex

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function.The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

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 score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
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 head0.075
GPT teacher head0.353
Teacher spread0.278 · 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

Citations153
Published2017
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicHearing, Cochlea, Tinnitus, GeneticsFrench-language works237,207