Multilevel models improve precision and speed of IC50 estimates

作者:Vis Daniel J*; Bombardelli Lorenzo; Lightfoot Howard; Iorio Francesco; Garnett Mathew J; Wessels Lodewyk F A
来源:Pharmacogenomics, 2016, 17(7): 691-700.
DOI:10.2217/pgs.16.15

摘要

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.

  • 出版日期2016-5