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Record W4414258422 · doi:10.1101/2025.09.07.674767

Uncovering Non-Monotonic Antagonistic and Synergistic Combinations (UNMASC), a robust method with applications to T cell differentiation <i>in vitro</i>

2025· preprint· en· W4414258422 on OpenAlexafffund
Geneviève Bistodeau-Gagnon, Yale S. Michaels, Morgan Craig

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
Topicvaccines and immunoinformatics approaches
Canadian institutionsCancerCare ManitobaUniversité de MontréalUniversity of ManitobaResearch Institute in Oncology and HematologyCentre Hospitalier Universitaire Sainte-Justine
FundersCanada Research Chairs
KeywordsCytokineProgenitor cellInduced pluripotent stem cellCellCellular differentiationT cell

Abstract

fetched live from OpenAlex

ABSTRACT Induced pluripotent stem cells (iPSCs) have been proposed as an alternative T cell source for CAR-T cell therapies, as they can be differentiated and matured into T cells in vitro using cytokines. These assays benefit from computational and mathematical models to design appropriate experimental protocols. However, models are limited by typical monotonic dose-responses, preventing them from being used for cytokine effects that are largely non-monotonic. To address this shortcoming, we developed Uncovering Non-Monotonic Antagonistic and Synergistic Combinations (UNMASC), a novel mathematical model describing non-monotonic dose-response surfaces of cytokine interactions that distinguishes synergy of efficacy and potency. We showed that our approach successfully recapitulates non-monotonic observed dose-response surfaces characterizing in vitro T cell progenitor differentiation. Our results highlighted cytokine combinations with antagonistic effects alone but synergistic in combination, particularly IL3 and IL7. Together, UNMASC accelerates the efficient cell generation assays and extends drug interaction surfaces to a broader range of dose-responses.

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 categoriesMeta-epidemiology (narrow)
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 score0.398
Threshold uncertainty score1.000

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 science0.0000.001
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 head0.008
GPT teacher head0.216
Teacher spread0.209 · 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.

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

Citations0
Published2025
Admission routes2
Has abstractyes

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