A community effort to assess and improve drug sensitivity prediction algorithms

James C Costello, Laura M Heiser, Elisabeth Georgii, Mehmet Gönen, Michael P Menden, Nicholas J Wang, Mukesh Bansal, Muhammad Ammad-ud-din, Petteri Hintsanen, Suleiman A Khan, John-patrick Mpindi, Olli Kallioniemi, Antti Honkela, Tero Aittokallio, Krister Wennerberg, James J Collins, Dan Gallahan, Dinah Singer, Julio Saez-rodriguez, Samuel KaskiJoe W Gray, Gustavo Stolovitzky, Madhuchhanda Bhattacharjee

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Abstract

Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms. The top-performing approaches modeled nonlinear relationships and incorporated biological pathway information. We found that gene expression microarrays consistently provided the best predictive power of the individual profiling data sets; however, performance was increased by including multiple, independent data sets. We discuss the innovations underlying the top-performing methodology, Bayesian multitask MKL, and we provide detailed descriptions of all methods. This study establishes benchmarks for drug sensitivity prediction and identifies approaches that can be leveraged for the development of new methods.
Original languageEnglish
Pages (from-to)1202-1212
JournalNature biotechnology
Volume32
Issue number12
Early online date1 Jun 2014
DOIs
Publication statusPublished - 1 Dec 2014

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