Integrating heterogeneous drug sensitivity data from cancer pharmacogenomic studies
Nikita V. Pozdeyev, Minjae Yoo, Ryan S. Mackie, Rebecca E. Schweppe, Aik Choon Tan, Bryan R. Haugen · Oncotarget · 2016
// Nikita Pozdeyev 1 , Minjae Yoo 1 , Ryan Mackie 1 , Rebecca E. Schweppe 1 , Aik Choon Tan 1, * , Bryan R. Haugen 1, * 1 Department of Medicine, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA * Two senior authors contributed equally to this work Correspondence to: Nikita Pozdeyev, email: [email protected] Keywords: database integration, drug sensitivity, pharmacogenomics, cancer, cell line Received: April 08, 2016 Accepted: May 29, 2016 Published: June 14, 2016 ABSTRACT The consistency of in vitro drug sensitivity data is of key importance for cancer pharmacogenomics. Previous attempts to correlate drug sensitivities from the large pharmacogenomics databases, such as the Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC), have produced discordant results. We developed a new drug sensitivity metric, the area under the dose response curve adjusted for the range of tested drug concentrations, which allows integration of heterogeneous drug sensitivity data from the CCLE, the GDSC, and the Cancer Therapeutics Response Portal (CTRP). We show that there is moderate to good agreement of drug sensitivity data for many targeted therapies, particularly kinase inhibitors. The results of this largest cancer cell line drug sensitivity data analysis to date are accessible through the online portal, which serves as a platform for high power pharmacogenomics analysis.