Revisiting inconsistency in large pharmacogenomic studies

BioRxiv : the Preprint Server for Biology
Zhaleh SafikhaniJohn Quackenbush

Abstract

Background: In 2012, two large pharmacogenomic studies, the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were published, each reported gene expression data and measure of drug response for a large number of drugs and hundreds of cell lines. In 2013, we published a comparative analysis that reported gene expression profiles for the 471 cell lines profiled in common by these two studies and dose response measurements for the 15 drugs profiled by both in those common cell lines. While we found good concordance in gene expression profiles, we found substantial inconsistency in the drug responses reported by the GDSC and CCLE projects. Our paper was widely discussed and we received extensive feedback on the comparisons we performed. This, along with the release of new data, prompted us to revisit our initial analysis. Here we present a new analysis using these expanded data in which we address the most significant suggestions for improvements on our published analysis: that drugs with different response characteristics should have been treated differently, that targeted therapies and broad cytotoxic drugs should have been treated differently in assessing consistency, that consistency of bot...Continue Reading

Related Concepts

Biological Markers
Gene Expression
Genome
Software Tools
Cell Line, Tumor
Cytotoxic agent
Tanespimycin
Experimentation
Drug Response
Comparative Analysis

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