An Ensemble Based Top Performing Approach for NCI-DREAM Drug Sensitivity Prediction Challenge

Abstract

We consider the problem of predicting sensitivity of cancer cell lines to new drugs based on supervised learning on genomic profiles. The genetic and epigenetic characterization of a cell line provides observations on various aspects of regulation including DNA copy number variations, gene expression, DNA methylation and protein abundance. To extract relevant information from the various data types, we applied a random forest based approach to generate sensitivity predictions from each type of data and combined the predictions in a linear regression model to generate the final drug sensitivity prediction. Our approach when applied to the NCI-DREAM drug sensitivity prediction challenge was a top performer among 47 teams and produced high accuracy predictions. Our results show that the incorporation of multiple genomic characterizations lowered the mean and variance of the estimated bootstrap prediction error. We also applied our approach to the Cancer Cell Line Encyclopedia database for sensitivity prediction and the ability to extract the top targets of an anti-cancer drug. The results illustrate the effectiveness of our approach in predicting drug sensitivity from heterogeneous genomic datasets. © 2014 Wan, Pal.