Multilevel models improve precision and speed of IC50 estimates.

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.

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.

MATERIALS & METHODS

We propose a multilevel mixed effects model that takes advantage of all available dose-response data.

CONCLUSION

The multilevel model yields a significant reduction of extreme IC50 estimates, an increase in precision and it runs orders of magnitude faster.

More about this publication

Pharmacogenomics
  • Volume 17
  • Issue nr. 7
  • Pages 691-700
  • Publication date 01-05-2016

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