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OMICS International, Journal of Pharmacogenomics and Pharmacoproteomics, 01(05), 2014

DOI: 10.4172/2153-0645.1000121

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Beyond IC50s: Towards Robust Statistical Methods for in vitro Association Studies

Journal article published in 2014 by Andrew Beam, Alison Motsinger-Reif ORCID, Alison MotsingerReif
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Cell line cytotoxicity assays have become increasingly popular approaches for genetic and genomic studies of differential cytotoxic response. There are an increasing number of success stories, but relatively little evaluation of the statistical approaches used in such studies. In the vast majority of these studies, concentration response is summarized using curve-fitting approaches, and then summary measure(s) are used as the phenotype in subsequent genetic association studies. The curve is usually summarized by a single parameter such as the curve's inflection point (e.g. the EC/IC50). Such modeling makes major assumptions and has statistical limitations that should be considered. In the current review, we discuss the limitations of the EC/IC50 as a phenotype in association studies, and highlight some potential limitations with a simulation experiment. Finally, we discuss some alternative analysis approaches that have been shown to be more robust.