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Assessment of network module identification across complex diseases

Sarvenaz Choobdar, Mehmet E. Ahsen, Jake Crawford, Mattia Tomasoni, Tao Fang, David Lamparter, Junyuan Lin, Benjamin Hescott, Xiaozhe Hu, Johnathan Mercer, Ted Natoli, Rajiv Narayan, The DREAM Module Identification Challenge Consortium, Aravind Subramanian, Jitao D. Zhang, 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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Tao Fang
5Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland
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David Lamparter
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland
2Swiss Institute of Bioinformatics, Lausanne, Switzerland
6Verge Genomics, San Francisco, CA, USA
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Junyuan Lin
7Department of Mathematics, Tufts University, Medford, MA, USA
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Benjamin Hescott
8College of Computer and Information Science, Northeastern University, Boston, MA, USA
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Xiaozhe Hu
7Department of Mathematics, Tufts University, Medford, MA, USA
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Johnathan Mercer
9Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
10Stanley Center at the Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Ted Natoli
11Broad Institute of Harvard and MIT, Cambridge, MA, USA
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Rajiv Narayan
11Broad Institute of Harvard and MIT, Cambridge, MA, USA
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12Full list of members appears at the end of the paper.
Aravind Subramanian
11Broad Institute of Harvard and MIT, Cambridge, MA, USA
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Jitao D. Zhang
5Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland
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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
13IBM T.J. Watson Research Center, Yorktown Heights, New York 10598, USA
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Zoltán Kutalik
2Swiss Institute of Bioinformatics, Lausanne, Switzerland
14Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
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Kasper Lage
9Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
10Stanley Center at the Broad Institute of MIT and Harvard, Cambridge, MA, USA
15Institute 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
16Department of Immunology, Tufts University School of Medicine, Medford, MA, USA
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Julio Saez-Rodriguez
17European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, UK
18RWTH 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
7Department 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
19Department 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
5Roche 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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Abstract

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 gene and protein networks remains poorly understood. We launched the “Disease Module Identification DREAM Challenge”, an open competition to comprehensively assess module identification methods across diverse protein-protein interaction, signaling, gene co-expression, homology, and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies (GWAS). Our critical assessment of 75 contributed module identification methods reveals novel top-performing algorithms, which recover complementary trait-associated modules. 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 July 30, 2019.
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Assessment of network module identification across complex diseases
Sarvenaz Choobdar, Mehmet E. Ahsen, Jake Crawford, Mattia Tomasoni, Tao Fang, David Lamparter, Junyuan Lin, Benjamin Hescott, Xiaozhe Hu, Johnathan Mercer, Ted Natoli, Rajiv Narayan, The DREAM Module Identification Challenge Consortium, Aravind Subramanian, Jitao D. Zhang, 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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Assessment of network module identification across complex diseases
Sarvenaz Choobdar, Mehmet E. Ahsen, Jake Crawford, Mattia Tomasoni, Tao Fang, David Lamparter, Junyuan Lin, Benjamin Hescott, Xiaozhe Hu, Johnathan Mercer, Ted Natoli, Rajiv Narayan, The DREAM Module Identification Challenge Consortium, Aravind Subramanian, Jitao D. Zhang, 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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