title: A community effort to assess and improve drug sensitivity prediction algorithms.
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.
authors.affiliation: 1] Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA. [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA. [3] [4].
authors.forename: James C
authors.initials: JC
authors.lastname: Costello
authors.affiliation: 1] Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA. [2].
authors.forename: Laura M
authors.initials: LM
authors.lastname: Heiser
authors.affiliation: 1] Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland. [2].
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Georgii
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gönen
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Menden
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wang
authors.affiliation: Department of Systems Biology, Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA.
authors.forename: Mukesh
authors.identifier: 0000000314816767
authors.initials: M
authors.lastname: Bansal
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ammad-ud-din
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Petteri
authors.initials: P
authors.lastname: Hintsanen
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland.
authors.forename: Suleiman A
authors.identifier: 0000000208234042
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: John-Patrick
authors.initials: JP
authors.lastname: Mpindi
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.identifier: 0000000232310332
authors.initials: O
authors.lastname: Kallioniemi
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Honkela
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
authors.affiliation: Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: Krister
authors.initials: K
authors.lastname: Wennerberg
authors.affiliation: 1] Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA. [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA. [3] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Gallahan
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dinah
authors.initials: D
authors.lastname: Singer
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.
authors.forename: Julio
authors.initials: J
authors.lastname: Saez-Rodriguez
authors.affiliation: 1] Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland. [2] Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kaski
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Joe W
authors.identifier: 0000000192256756
authors.initials: JW
authors.lastname: Gray
authors.affiliation: IBM T.J. Watson Research Center, IBM, Yorktown Heights, New York, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stolovitzky
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D040901:Proteomics / Q000379:methods
chemical_list: D000970:Antineoplastic Agents