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Publication — IRIC

RECOVER identifies synergistic drug combinations in vitro through sequential model optimization.

For large libraries of small molecules, exhaustive combinatorial chemical screens become infeasible to perform when considering a range of disease models, assay conditions, and dose ranges. Deep learning models have achieved state-of-the-art results in silico for the prediction of synergy scores. However, databases of drug combinations are biased toward synergistic agents and results do not generalize out of distribution. During 5 rounds of experimentation, we employ sequential model optimization with a deep learning model to select drug combinations increasingly enriched for synergism and active against a cancer cell line-evaluating only ∼5% of the total search space. Moreover, we find that learned drug embeddings (using structural information) begin to reflect biological mechanisms. In silico benchmarking suggests search queries are ∼5-10× enriched for highly synergistic drug combinations by using sequential rounds of evaluation when compared with random selection or ∼3× when using a pretrained model.

Publication date
October 4, 2023
Principal Investigators
Bertin P, Rector-Brooks J, Sharma D, Gaudelet T, Anighoro A, Gross T, Martínez-Peña F, Tang EL, Suraj MS, Regep C, Hayter JBR, Korablyov M, Valiante N, van der Sloot A, Tyers M, Roberts CES, Bronstein MM, Lairson LL, Taylor-King JP, Bengio Y
PubMed reference
Cell Rep Methods 2023;3(10):100599
PubMed ID
Mila, the Quebec AI Institute, Montreal, QC, Canada.