title: A community computational challenge to predict the activity of pairs of compounds.
abstract: Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing. We highlight similarities between the methods. Although the accuracy of predictions was not optimal, we find that computational prediction of compound-pair activity is possible, and that community challenges can be useful to advance the field of in silico compound-synergy prediction.
authors.affiliation: 1] Department of Systems Biology, Columbia University, New York, New York, USA. [2] 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: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jichen
authors.initials: J
authors.lastname: Yang
authors.affiliation: Columbia Genome Center, High Throughput Screening Facility, Columbia University, New York, New York, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Karan
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Menden
authors.affiliation: Howard Hughes Medical Institute, Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, Boston, Massachusetts, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Costello
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Allen
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Beibei
authors.initials: B
authors.lastname: Chen
authors.affiliation: 1] Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [2] Simmons Comprehensive Cancer Center, University of Texas, Southwestern Medical Center, Texas, USA.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Tao
authors.identifier: 000000024355149X
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Heiser
authors.affiliation: Columbia Genome Center, High Throughput Screening Facility, Columbia University, New York, New York, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Realubit
authors.affiliation: Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
authors.forename: Michela
authors.identifier: 0000000216929178
authors.initials: M
authors.lastname: Mattioli
authors.affiliation: 1] Department of Systems Biology, Columbia University, New York, New York, USA. [2] Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA.
authors.forename: Mariano J
authors.initials: MJ
authors.lastname: Alvarez
authors.affiliation: 1] Department of Systems Biology, Columbia University, New York, New York, USA. [2] Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gallahan
authors.affiliation: Division of Cancer Biology, National Cancer Institute, 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, Hinxton, Cambridge, UK.
authors.forename: Julio
authors.identifier: 0000000285528976
authors.initials: J
authors.lastname: Saez-Rodriguez
authors.affiliation: 1] Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [2] Simmons Comprehensive Cancer Center, University of Texas, Southwestern Medical Center, Texas, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: IBM Computational Biology Center, IBM, T.J. Watson Research Center, Yorktown Heights, New York, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stolovitzky
authors.affiliation: 1] Department of Systems Biology, Columbia University, New York, New York, USA. [2] Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA. [3] Department of Biomedical Informatics, Columbia University, New York, New York, USA. [4] Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA. [5] Institute for Cancer Genetics, Columbia University, New York, New York, USA. [6] Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Califano
mesh_terms: D000465:Algorithms; D001402:B-Lymphocytes / Q000187:drug effects; D003198:Computer Simulation; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans
chemical_list: D004338:Drug Combinations