Cancer biomarker discovery is improved by accounting for variability in general levels of drug sensitivity in pre-clinical models

Paul Geeleher, Nancy J. Cox, R. Stephanie Huang

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We show that variability in general levels of drug sensitivity in pre-clinical cancer models confounds biomarker discovery. However, using a very large panel of cell lines, each treated with many drugs, we could estimate a general level of sensitivity to all drugs in each cell line. By conditioning on this variable, biomarkers were identified that were more likely to be effective in clinical trials than those identified using a conventional uncorrected approach. We find that differences in general levels of drug sensitivity are driven by biologically relevant processes. We developed a gene expression based method that can be used to correct for this confounder in future studies.

Original languageEnglish (US)
Article number190
JournalGenome biology
Volume17
Issue number1
DOIs
StatePublished - Sep 21 2016

Bibliographical note

Funding Information:
This study was supported by the NIH/NIGMS grant UO1GM61393, Circle of Service Foundation Early Career Investigator award, University of Chicago CTSA core subsidy grant, and a Conquer Cancer Foundation of ASCO Translational Research Professorship award In Memory of Merrill J. Egorin, MD (awarded to Dr. MJ Ratain). RSH also received support from NIH/NIGMS grant K08GM089941, NIH/NCI grant R21 CA139278, University of Chicago Support Grant (#P30 CA14599), Breast Cancer SPORE Career Development Award (CA125183) and the National Center for Advancing Translational Sciences of the NIH (UL1RR024999). PG received support from the Chicago Biomedical Consortium grant PDR-020.

Publisher Copyright:
© 2016 The Author(s).

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