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.

CONCLUSION

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

MATERIALS & METHODS

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

More about this publication

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

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