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Record W4321116366 · doi:10.1016/j.stemcr.2023.01.008

In silico discovery of small molecules for efficient stem cell differentiation into definitive endoderm

2023· article· en· W4321116366 on OpenAlexafffund
Gherman Novakovsky, Shugo Sasaki, Oriol Fornés, Meltem E. Omur, Helen Huang, Carmen Bayly, Dahai Zhang, Nathaniel C. Lim, Artem Cherkasov, Paul Pavlidis, Sara Mostafavi, Francis C. Lynn, Wyeth W. Wasserman

Bibliographic record

VenueStem Cell Reports · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPluripotent Stem Cells Research
Canadian institutionsUniversity of British Columbia HospitalCanada's Michael Smith Genome Sciences CentreBC Children's HospitalUniversity of British Columbia
FundersBreakthrough T1D CanadaNational Institute of Mental HealthNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchBC Children's HospitalMichael Smith Health Research BCBC Children’s Hospital FoundationManpei Suzuki Diabetes FoundationUniversity of British ColumbiaStem Cell NetworkNational Institutes of HealthChildren's Hospital FoundationJuvenile Diabetes Research Foundation CanadaJuvenile Diabetes Research Foundation United States of America
KeywordsEndodermBiologyIn silicoStem cellEmbryonic stem cellCellular differentiationComputational biologyRegenerative medicineCell biologyGeneticsGene

Abstract

fetched live from OpenAlex

Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by inclusion of this compound achieves the same differentiation efficiency with a 90% cost reduction. The presented in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols.

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 score0.004
Threshold uncertainty score0.822

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 head0.017
GPT teacher head0.252
Teacher spread0.235 · 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

Citations21
Published2023
Admission routes2
Has abstractyes

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