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Open Community Challenge Reveals Molecular Network Modules with Key Roles in Diseases

Sarvenaz Choobdar, Mehmet E. Ahsen, Jake Crawford, Mattia Tomasoni, David Lamparter, Junyuan Lin, Benjamin Hescott, Xiaozhe Hu, Johnathan Mercer, Ted Natoli, Rajiv Narayan, The DREAM Module Identification Challenge Consortium, Aravind Subramanian, Gustavo Stolovitzky, Zoltán Kutalik, Kasper Lage, Donna K. Slonim, Julio Saez-Rodriguez, Lenore J. Cowen, Sven Bergmann, Daniel Marbach
doi: https://doi.org/10.1101/265553
Sarvenaz Choobdar
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
2Swiss Institute of Bioinformatics, Lausanne, Switzerland.
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Mehmet E. Ahsen
3Icahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Jake Crawford
4Department of Computer Science, Tufts University, Medford, MA, USA.
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Mattia Tomasoni
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
2Swiss Institute of Bioinformatics, Lausanne, Switzerland.
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David Lamparter
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
2Swiss Institute of Bioinformatics, Lausanne, Switzerland.
5Verge Genomics, San Francisco, CA, USA.
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Junyuan Lin
6Department of Mathematics, Tufts University, Medford, MA, USA.
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Benjamin Hescott
7College of Computer and Information Science, Northeastern University, Boston, MA, USA.
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Xiaozhe Hu
6Department of Mathematics, Tufts University, Medford, MA, USA.
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Johnathan Mercer
8Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
9Stanley Center at the Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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Ted Natoli
10Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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Rajiv Narayan
10Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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11Full list of members appears at the end of the paper.
Aravind Subramanian
10Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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Gustavo Stolovitzky
3Icahn Institute for Genomics and Multiscale Biology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
12IBM T.J. Watson Research Center, Yorktown Heights, New York 10598, USA.
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Zoltán Kutalik
2Swiss Institute of Bioinformatics, Lausanne, Switzerland.
13Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.
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Kasper Lage
8Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
9Stanley Center at the Broad Institute of MIT and Harvard, Cambridge, MA, USA.
14Institute for Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark.
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Donna K. Slonim
4Department of Computer Science, Tufts University, Medford, MA, USA.
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Julio Saez-Rodriguez
15European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, UK
16RWTH Aachen University, Faculty of Medicine, Joint Research Center for Computational Biomedicine, Aachen, Germany
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Lenore J. Cowen
4Department of Computer Science, Tufts University, Medford, MA, USA.
6Department of Mathematics, Tufts University, Medford, MA, USA.
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Sven Bergmann
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
2Swiss Institute of Bioinformatics, Lausanne, Switzerland.
17Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa
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  • For correspondence: sven.bergmann@unil.ch daniel.marbach.dm1@roche.com
Daniel Marbach
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
2Swiss Institute of Bioinformatics, Lausanne, Switzerland.
18Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland.
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  • For correspondence: sven.bergmann@unil.ch daniel.marbach.dm1@roche.com
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Summary

Identification of modules in molecular networks is at the core of many current analysis methods in biomedical research. However, how well different approaches identify disease-relevant modules in different types of networks remains poorly understood. We launched the “Disease Module Identification DREAM Challenge”, an open competition to comprehensively assess module identification methods across diverse gene, protein and signaling networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies (GWAS). While a number of approaches were successful in terms of discovering complementary trait-associated modules, consensus predictions derived from the challenge submissions performed best. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets and correctly prioritize candidate disease genes. This community challenge establishes benchmarks, tools and guidelines for molecular network analysis to study human disease biology (https://synapse.org/modulechallenge).

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 15, 2018.
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Open Community Challenge Reveals Molecular Network Modules with Key Roles in Diseases
Sarvenaz Choobdar, Mehmet E. Ahsen, Jake Crawford, Mattia Tomasoni, David Lamparter, Junyuan Lin, Benjamin Hescott, Xiaozhe Hu, Johnathan Mercer, Ted Natoli, Rajiv Narayan, The DREAM Module Identification Challenge Consortium, Aravind Subramanian, Gustavo Stolovitzky, Zoltán Kutalik, Kasper Lage, Donna K. Slonim, Julio Saez-Rodriguez, Lenore J. Cowen, Sven Bergmann, Daniel Marbach
bioRxiv 265553; doi: https://doi.org/10.1101/265553
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Open Community Challenge Reveals Molecular Network Modules with Key Roles in Diseases
Sarvenaz Choobdar, Mehmet E. Ahsen, Jake Crawford, Mattia Tomasoni, David Lamparter, Junyuan Lin, Benjamin Hescott, Xiaozhe Hu, Johnathan Mercer, Ted Natoli, Rajiv Narayan, The DREAM Module Identification Challenge Consortium, Aravind Subramanian, Gustavo Stolovitzky, Zoltán Kutalik, Kasper Lage, Donna K. Slonim, Julio Saez-Rodriguez, Lenore J. Cowen, Sven Bergmann, Daniel Marbach
bioRxiv 265553; doi: https://doi.org/10.1101/265553

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