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Record W2993946495 · doi:10.1016/j.stemcr.2019.11.003

Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation

2019· article· en· W2993946495 on OpenAlexafffundabout
Matthew R. Hildebrandt, Miriam S. Reuter, Wei Wei, Naeimeh Tayebi, Jiajie Liu, Sazia Sharmin, Jaap Mulder, Lee Stephen Lesperance, Patrick M. Brauer, Rebecca S.F. Mok, Caroline Kinnear, Alina Piekna, Asli Romm, Jennifer Howe, Peter Pasceri, Guoliang Meng, Matthew Rozycki, Deivid C. Rodrigues, Michael J. Szego, Juan Carlos Zúñiga‐Pflücker, Michele K. Anderson, Steven A. Prescott, Norman D. Rosenblum, Binita M. Kamath, Seema Mital, Stephen W. Scherer, James Ellis

Bibliographic record

VenueStem Cell Reports · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPluripotent Stem Cells Research
Canadian institutionsPublic Health OntarioUniversity of TorontoSunnybrook Health Science CentreSickKids FoundationHospital for Sick Children
FundersNational Institute of Allergy and Infectious DiseasesNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchCanada First Research Excellence FundHuman Genome SciencesOntario Brain InstituteCentre for Jewish Studies, University of TorontoHeart and Stroke Foundation of CanadaGlaxoSmithKlineHospital for Sick Children
KeywordsBiologyInduced pluripotent stem cellComputational biologyOrganoidPhenotypeGenomeDiseaseGeneticsBioinformaticsGeneEmbryonic stem cellInternal medicine

Abstract

fetched live from OpenAlex

Induced pluripotent stem cells (iPSC) derived from healthy individuals are important controls for disease-modeling studies. Here we apply precision health to create a high-quality resource of control iPSCs. Footprint-free lines were reprogrammed from four volunteers of the Personal Genome Project Canada (PGPC). Multilineage-directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users demonstrated versatility by generating kidney organoids, T lymphocytes, and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited the expected hypertrophic phenotype. Whole-genome sequencing-based annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harbored at least one pre-existing or acquired variant with cardiac, neurological, or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cells from six tissues for disease modeling, and variant-preferred healthy control lines were identified for specific disease settings.

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)0.003
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation 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: none
Teacher disagreement score0.007
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0070.004

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 head0.268
Teacher spread0.257 · 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 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

Citations50
Published2019
Admission routes3
Has abstractyes

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