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PMID: 25419740 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A community computational challenge to predict the activity of pairs of compounds.

Nature biotechnology ·Vol. 32 ·No. 12 ·2014-12-00 ·Pages 1213-22

Bansal M, Yang J, Karan C, Menden MP, Costello JC, Tang H, Xiao G, Li Y, Allen J, Zhong R, Chen B, Kim M, Wang T, Heiser LM, Realubit R, Mattioli M, Alvarez MJ, Shen Y, NCI-DREAM Community, Gallahan D, Singer D, Saez-Rodriguez J, Xie Y, Stolovitzky G, Califano A, NCI-DREAM Community

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.

MeSH Terms
Algorithms B-Lymphocytes/drug effects Computer Simulation Drug Combinations Drug Synergism Humans
Chemicals
Drug Combinations
Authors & Affiliations
26 authors, click to expand affiliations / ORCID
Bansal Mukesh ORCID
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.
Yang Jichen
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Karan Charles
Columbia Genome Center, High Throughput Screening Facility, Columbia University, New York, New York, USA.
Menden Michael P
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Costello James C
Howard Hughes Medical Institute, Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, Boston, Massachusetts, USA.
Tang Hao
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Xiao Guanghua
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Li Yajuan
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Allen Jeffrey
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Zhong Rui
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Chen Beibei
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Kim Minsoo
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.
Wang Tao ORCID
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Heiser Laura M
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA.
Realubit Ronald
Columbia Genome Center, High Throughput Screening Facility, Columbia University, New York, New York, USA.
Mattioli Michela ORCID
Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
Alvarez Mariano J
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.
Shen Yao
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.
NCI-DREAM Community
Gallahan Daniel
Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA.
Singer Dinah
Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA.
Saez-Rodriguez Julio ORCID
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Xie Yang
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.
Stolovitzky Gustavo
IBM Computational Biology Center, IBM, T.J. Watson Research Center, Yorktown Heights, New York, USA.
Califano Andrea
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.
NCI-DREAM Community
Investigators
98 investigators, click to expand
Abbuehl Jean-Paul
Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Allen Jeffrey
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Altman Russ B
Departments of Genetics, Stanford University, Stanford, California, USA.
Balcome Shawn
University of Minnesota, Minneapolis, Minnesota, USA.
Bansal Mukesh
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.
Bell Ana
1] Department of Computer Science, Princeton University, Princeton, New Jersey, USA. [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Bender Andreas
Unilever Centre, Cambridge University, Cambridge, UK.
Berger Bonnie
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts, USA.
Bernard Jonathan
Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Bieberich Andrew A
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, W. Lafayette, Indiana, USA.
Borboudakis Giorgos
1] Computer Science Department, University of Crete, Crete, Greece. [2] Institute of Computer Science, FORTH, Crete, Greece.
Califano Andrea
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 Cente
Chan Christina
1] Department of Computer Science and Engineering, Michigan State University, East Lansing, Michigan, USA. [2] Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan, USA. [3] Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA.
Chen Beibei
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Chen Ting-Huei
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA.
Choi Jaejoon
Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Coelho Luis Pedro
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Costello James C
Howard Hughes Medical Institute, Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, Boston, Massachusetts, USA.
Creighton Chad J
Department of Medicine, Dan L. Duncan Center Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.
Dampier Will
Center for Integrated Bioinformatics, Drexel University, Philadelphia, Pennsylvania, USA.
Davisson V Jo
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, W. Lafayette, Indiana, USA.
Deshpande Raamesh
University of Minnesota, Minneapolis, Minnesota, USA.
Diao Lixia
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Di Camillo Barbara
Department of Information Engineering, University of Padova, Padova, Italy.
Dundar Murat
Department of Computer and Information Science, IUPUI, Indianapolis, Indiana, USA.
Ertel Adam
Jefferson Kimmel Cancer Center, Philadelphia, Pennsylvania, USA.
Gallahan Daniel
Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA.
Goswami Chirayu P
Center for Computational Biology and Bioinformatics, IU School of Medicine, Indianapolis, Indiana, USA.
Gottlieb Assaf
Departments of Genetics, Stanford University, Stanford, California, USA.
Gould Michael N
Department of Oncology and Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin, USA.
Goya Jonathan
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Grau Michael
Department of Physics, University of Marburg, Marburg, Germany.
Gray Joe W
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA.
Heiser Laura M
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, USA.
Hejase Hussein A
Department of Computer Science and Engineering, Michigan State University, East Lansing, Michigan, USA.
Hoffmann Michael F
Department of Oncology and Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin, USA.
Homicsko Krisztian
Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Homilius Max
1] Department of Computer Science, Princeton University, Princeton, New Jersey, USA. [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Hwang Woochang
Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Ijzerman Adriaan P
Leiden Academic Center for Drug Research, University of Leiden, Leiden, the Netherlands.
Kallioniemi Olli
Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Karacali Bilge
Izmir Institute of Technology, Izmir, Turkey.
Karan Charles
Columbia Genome Center, High Throughput Screening Facility, Columbia University, New York, New York, USA.
Kaski Samuel
1] Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland. [2] Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland.
Kim Junho
Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Kim Minsoo
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.
Krishnan Arjun
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Lee Junehawk
1] Korea Advanced Institute of Science and Technology, Daejeon, Korea. [2] Korea Institute of Science and Technology Information, Daejeon, Korea.
Lee Young-Suk
1] Department of Computer Science, Princeton University, Princeton, New Jersey, USA. [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Lenselink Eelke B
Leiden Academic Center for Drug Research, University of Leiden, Leiden, the Netherlands.
Lenz Peter
Department of Physics, University of Marburg, Marburg, Germany.
Li Lang
Center for Computational Biology and Bioinformatics, IU School of Medicine, Indianapolis, Indiana, USA.
Li Jun
1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] CAS-MPG Partner Institute for Computational Biology, Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
Li Yajuan
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Liang Han
1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Mattioli Michela
Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
Menden Michael P
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Mpindi John-Patrick
Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Myers Chad L
University of Minnesota, Minneapolis, Minnesota, USA.
Newton Michael A
Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin, USA.
Overington John P
European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Parkkinen Juuso
Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, Espoo, Finland.
Prill Robert J
IBM Almaden Research Center, San Jose, California, USA.
Peng Jian
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts, USA.
Pestell Richard
Jefferson Kimmel Cancer Center, Philadelphia, Pennsylvania, USA.
Qiu Peng
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Rajwa Bartek
Bindley Bioscience Center, Purdue University, W. Lafayette, Indiana, USA.
Realubit Ronald
Columbia Genome Center, High Throughput Screening Facility, Columbia University, New York, New York, USA.
Sadanandam Anguraj
Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Saez-Rodriguez Julio
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Sambo Francesco
Department of Information Engineering, University of Padova, Padova, Italy.
Singer Dinah
Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA.
Stolovitzky Gustavo
IBM Computational Biology Center, IBM, T.J. Watson Research Center, Yorktown Heights, New York, USA.
Sridhar Arvind
Embedded Systems Laboratory (ESL), Institute of Electrical Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), Laussane, Switzerland.
Sun Wei
1] Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA. [2] Department of Genetics, UNC Chapel Hill, Chapel Hill, North Carolina, USA.
Tang Hao
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Toffolo Gianna M
Department of Information Engineering, University of Padova, Padova, Italy.
Tozeren Aydin
Center for Integrated Bioinformatics, Drexel University, Philadelphia, Pennsylvania, USA.
Troyanskaya Olga G
1] Department of Computer Science, Princeton University, Princeton, New Jersey, USA. [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Tsamardinos Ioannis
1] Computer Science Department, University of Crete, Crete, Greece. [2] Institute of Computer Science, FORTH, Crete, Greece.
van Vlijmen Herman W T
Janssen Pharmaceutica, Beerse, Belgium.
Wang Tao
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Wang Wen
University of Minnesota, Minneapolis, Minnesota, USA.
Wegner Joerg K
Janssen Pharmaceutica, Beerse, Belgium.
Wennerberg Krister
Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
van Westen Gerard J P
European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Xia Tian
University of Minnesota, Minneapolis, Minnesota, USA.
Xiao Guanghua
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Xie Yang
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.
Yang Jichen
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Yang Yang
1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Division of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Yao Victoria
1] Department of Computer Science, Princeton University, Princeton, New Jersey, USA. [2] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Yuan Yuan
1] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Zeng Haoyang
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, Massachusetts, USA.
Zhang Shihua
National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.
Zhao Junfei
National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.
Zhou Jian
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA .
Zhong Rui
Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
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Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.3052
Published
2014-12-00
Epub
2014-00-17
Pages
1213-22
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC4399794
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · 5U54CA121852-08 · United States
NCI NIH HHS · U01 CA168426 · United States
Wellcome Trust · 104104 · United Kingdom
NCI NIH HHS · 5R01CA152301 · United States
NHLBI NIH HHS · U01 HL111566 · United States
NCI NIH HHS · R01 CA152301 · United States
NCI NIH HHS · P50 CA058207 · United States
NCI NIH HHS · U54 CA121852 · United States
NHLBI NIH HHS · 3U01HL111566-02 · United States
NCI NIH HHS · U54 CA112970 · United States
NIGMS NIH HHS · R01 GM071966 · United States
NCI NIH HHS · U01 CA164184 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM081871 · United States
NCI NIH HHS · 1U01CA164184-02 · United States
NHGRI NIH HHS · T32 HG003284 · United States
External Links
PubMed source DOI: 10.1038/nbt.3052 PMC Full Text View journal details
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