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Record W4412741575 · doi:10.1126/sciadv.adt1851

Machine learning-assisted exploration of multidrug-drug administration regimens for organoid arrays

2025· article· en· W4412741575 on OpenAlexaff
Ilya Yakavets, Sina Kheiri, Jennifer Cruickshank, Riley J. Hickman, Faeze Rakhshani, Matteo Aldeghi, Ella Miray Rajaonson, Edmond W. K. Young, Alán Aspuru‐Guzik, David W. Cescon, Eugenia Kumacheva

Bibliographic record

VenueScience Advances · 2025
Typearticle
Languageen
FieldEngineering
Topic3D Printing in Biomedical Research
Canadian institutionsCanadian Institute for Advanced ResearchVector InstituteCanada Research ChairsPrincess Margaret Cancer CentreUniversity Health NetworkUniversity of Toronto
Fundersnot available
KeywordsDrugMedicinePharmacologyOrganoidRegimenCombination therapyDrug discoveryDrug administrationEfficacyCancerPersonalized medicineBioinformaticsInternal medicineBiologyNeuroscience

Abstract

fetched live from OpenAlex

Combination therapies enhance the therapeutic effect of cancer treatment; however, identifying effective interdependent doses, durations, and sequences of multidrug administration regimens is a time- and labor-intensive task. Here, we integrated machine learning, automation, and large microfluidic arrays of cancer spheroids or patient-derived organoids formed in a tissue-mimetic hydrogel to achieve notable acceleration of the discovery of effective multidrug administration regimens. For the clinically approved drug combination, we found a sequential administration regimen leading to a substantial reduction in the total drug dose, in comparison with concurrent drug supply, both at comparable drug efficacy. For the drugs that are currently under clinical development, we found a synergistic effect of concurrently administered drugs and showed that the synergy diminishes for the sequential drug supply. The developed strategy holds promise for the discovery of effective combination therapies for advanced cancer treatment, including personalized chemotherapies.

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)0.000
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: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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)0.0010.000

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 head0.024
GPT teacher head0.332
Teacher spread0.308 · 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 designSimulation or modeling
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

Citations16
Published2025
Admission routes1
Has abstractyes

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