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In: Journal of Differential Equations. - 0022-0396. ; 197:1, s. 73-84
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- We present an approach for proving the global existence of classical solutions of certain quasilinear parabolic systems with homogeneous Dirichlet boundary conditions in bounded domains with a smooth boundary. (C) 2003 Elsevier Inc. All rights reserved.
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
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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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Fast eQTL Analysis for Twin Studies
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In: Genetic epidemiology. - : Wiley. - 1098-2272 .- 0741-0395. ; 39:5, s. 357-365
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