Daniel J Vis1,2, Lorenzo Bombardelli3, Howard Lightfoot4, Francesco Iorio5, Mathew J Garnett4, Lodewyk Fa Wessels1,2,6. 1. Center for Personalized Cancer Treatment (CPCT), Utrecht/Amsterdam, The Netherlands. 2. Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Wellcome Trust Sanger Institute, Cambridge, United Kingdom. 5. European Molecular Biology Laboratory - European Bioinformatics Institute, Cambridge, United Kingdom. 6. Technical University Delft, Delft, The Netherlands.
Abstract
AIM: Experimental variation in dose-response data of drugs tested on cell lines result in inaccuracies in the estimate of a key drug sensitivity characteristic: the IC50. We aim to improve the precision of the half-limiting dose (IC50) estimates by simultaneously employing all dose-responses across all cell lines and drugs, rather than using a single drug-cell line response. MATERIALS & METHODS: We propose a multilevel mixed effects model that takes advantage of all available dose-response data. RESULTS: The new estimates are highly concordant with the currently used Bayesian model when the data are well behaved. Otherwise, the multilevel model is clearly superior. CONCLUSION: The multilevel model yields a significant reduction of extreme IC50 estimates, an increase in precision and it runs orders of magnitude faster.
AIM: Experimental variation in dose-response data of drugs tested on cell lines result in inaccuracies in the estimate of a key drug sensitivity characteristic: the IC50. We aim to improve the precision of the half-limiting dose (IC50) estimates by simultaneously employing all dose-responses across all cell lines and drugs, rather than using a single drug-cell line response. MATERIALS & METHODS: We propose a multilevel mixed effects model that takes advantage of all available dose-response data. RESULTS: The new estimates are highly concordant with the currently used Bayesian model when the data are well behaved. Otherwise, the multilevel model is clearly superior. CONCLUSION: The multilevel model yields a significant reduction of extreme IC50 estimates, an increase in precision and it runs orders of magnitude faster.
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