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Record W4210403184 · doi:10.1016/j.isci.2022.103858

Identification of new ETV6 modulators through a high-throughput functional screening

2022· article· en· W4210403184 on OpenAlexafffund
Benjamin Neveu, Chantal Richer, Pauline Cassart, Maxime Caron, Camille Jimenez‐Cortes, Pascal St-Onge, Claire Fuchs, Nicolas Garnier, Stéphane Gobeil, Daniel Sinnett

Bibliographic record

VenueiScience · 2022
Typearticle
Languageen
FieldMedicine
TopicAcute Lymphoblastic Leukemia research
Canadian institutionsUniversité LavalMcGill UniversityUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersCentre de recherche du CHU Sainte-JustineFonds de recherche du Québec – Nature et technologiesUniversité de MontréalTerry Fox Research InstituteCanada Foundation for InnovationCole FoundationCanadian Institutes of Health ResearchMcGill University Health CentreMcGill University
KeywordsETV6Gene silencingBiologyJUNBChromatinGeneTranscriptional regulationComputational biologyTranscription factorGeneticsCancer researchChromosomal translocation

Abstract

fetched live from OpenAlex

ETV6 transcriptional activity is critical for proper blood cell development in the bone marrow. Despite the accumulating body of evidence linking ETV6 malfunction to hematological malignancies, its regulatory network remains unclear. To uncover genes that modulate ETV6 repressive transcriptional activity, we performed a specifically designed, unbiased genome-wide shRNA screen in pre-B acute lymphoblastic leukemia cells. Following an extensive validation process, we identified 13 shRNAs inducing overexpression of ETV6 transcriptional target genes. We showed that the silencing of AKIRIN1 , COMMD9 , DYRK4 , JUNB, and SRP72 led to an abrogation of ETV6 repressive activity. We identified critical modulators of the ETV6 function which could participate in cellular transformation through the ETV6 transcriptional network.

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)0.000
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: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.043
GPT teacher head0.312
Teacher spread0.269 · 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

Citations6
Published2022
Admission routes2
Has abstractyes

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