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Pharmacogenomics. 2016 May;17(7):691-700. doi: 10.2217/pgs.16.15. Epub 2016 May 16.

Multilevel models improve precision and speed of IC50 estimates.

Author information

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.

KEYWORDS:

IC50; doseā€“response; mixed effects; nonlinear

PMID:
27180993
DOI:
10.2217/pgs.16.15
[Indexed for MEDLINE]
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