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- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Ishola, Mofoluwake M., et al.
(author)
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Simultaneous saccharification, filtration and fermentation (SSFF) : A novel method for bioethanol production from lignocellulosic biomass
- 2013
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In: Bioresource Technology. - : Elsevier. - 0960-8524 .- 1873-2976. ; 133, s. 68-73
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Journal article (peer-reviewed)abstract
- Simultaneous saccharification, filtration and fermentation (SSFF) was developed for lignocellulosic ethanol production. In SSFF, pretreated lignocellulosic material is enzymatically hydrolyzed in a reactor, while the suspension is continuously pumped through a cross-flow membrane. The retentate goes back to the hydrolysis vessel, while a clear sugar-rich filtrate continuously perfuses through the fermentation vessel before it is pumped back to the hydrolysis vessel. The capacity and life span of the cross-flow filter module was examined for 4 weeks using enzymatically hydrolyzed slurry, initially with 14.4% suspended solids, without clogging or fouling. An ethanol yield of 85.0% of the theoretical yield was obtained in SSFF and a flocculating strain of Saccharomyces cerevisiae was successfully reused for five cultivations of SSFF.
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