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Record W4310702752 · doi:10.1038/s41598-022-19710-7

Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes

2022· article· en· W4310702752 on OpenAlexaff
Kendall Higgins, Bret A. Moore, Zorana Berberovic, Hibret A. Adissu, Mohammad Eskandarian, Ann M. Flenniken, Andy Shao, Denise M. Imai, Dave Clary, Louise Lanoue, Susan Newbigging, Lauryl M. J. Nutter, David J. Adams, Fátima Bosch, Robert E. Braun, Steve D. M. Brown, Mary E. Dickinson, Michael S. Dobbie, Paul Flicek, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D. Heaney, Yann Hérault, Martin Hrabě de Angelis, Hsian‐Jean Chin, Fabio Mammano, Chuan Qin, Toshihiko Shiroishi, Radislav Sedláček, Je Kyung Seong, Ying Xu, Arthur L. Beaudet, Bob Braun, Natasha A. Karp, Ann‐Marie Mallon, Terrence F. Meehan, Yuichi Obata, Helen Parkinson, Damian Smedley, Glauco P. Tocchini‐Valentini, Sara Wells, K. C. Kent Lloyd, Colin McKerlie, Ala Moshiri

Bibliographic record

VenueScientific Reports · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and Kidney Cyst Diseases
Canadian institutionsHospital for Sick ChildrenToronto Centre for PhenogenomicsLunenfeld-Tanenbaum Research InstituteSickKids FoundationMount Sinai Hospital
FundersNational Eye InstituteNational Human Genome Research InstituteNational Institutes of Health
KeywordsCiliopathyCiliopathiesBiologyCiliumPhenotypeGeneGeneticsCandidate geneGene knockoutCiliogenesisKnockout mouseComputational biology

Abstract

fetched live from OpenAlex

We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes." From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. Histological and morphological evidence of phenotypes found in ciliopathies in knockout mouse lines are presented as examples (genes Abi2, Wdr62, Ap4e1, Dync1li1, and Prkab1). Phenotyping data and descriptions generated on IMPC mouse line are useful for mechanistic studies, target discovery, rare disease diagnosis, and preclinical therapeutic development trials. Here we demonstrate the effective use of the IMPC phenotype data to uncover genes with no previous role in ciliary biology, which may be clinically relevant for identification of novel disease genes implicated in ciliopathies.

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)0.001
metaresearch head score (Gemma)0.001
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 score0.007
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0070.004
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.002

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 head0.008
GPT teacher head0.235
Teacher spread0.227 · 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
Published2022
Admission routes1
Has abstractyes

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