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The Network Zoo: a multilingual package for the inference and analysis of biological networks

View ORCID ProfileMarouen Ben Guebila, View ORCID ProfileTian Wang, View ORCID ProfileCamila M. Lopes-Ramos, View ORCID ProfileViola Fanfani, View ORCID ProfileDeborah Weighill, Rebekka Burkholz, View ORCID ProfileDaniel Schlauch, View ORCID ProfileJoseph N. Paulson, View ORCID ProfileMichael Altenbuchinger, Abhijeet Sonanwane, James Lim, Genis Calderer, View ORCID ProfileDavid van Ijzendoorn, View ORCID ProfileDaniel Morgan, View ORCID ProfileAlessandro Marin, View ORCID ProfileCho-Yi Chen, Alex Song, View ORCID ProfileKate Shutta, View ORCID ProfileDawn DeMeo, View ORCID ProfileMegha Padi, John Platig, View ORCID ProfileMarieke L. Kuijjer, View ORCID ProfileKimberly Glass, View ORCID ProfileJohn Quackenbush
doi: https://doi.org/10.1101/2022.05.30.494077
Marouen Ben Guebila
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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  • ORCID record for Marouen Ben Guebila
Tian Wang
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
2Biology Department, Boston College, Chestnut Hill, MA, USA
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Camila M. Lopes-Ramos
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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Viola Fanfani
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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  • ORCID record for Viola Fanfani
Deborah Weighill
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
4Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA
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Rebekka Burkholz
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
5CISPA Helmholtz Center for Information Security, Saarbrücken, Germany
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Daniel Schlauch
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
6Genospace, LLC, Boston, MA, USA
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Joseph N. Paulson
7Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, USA
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Michael Altenbuchinger
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
8Department of Medical Bioinformatics, University Medical Center Göttingen, Göttingen, Germany
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Abhijeet Sonanwane
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
9Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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James Lim
10Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA
11Monoceros Biosystems, LLC, San Diego, CA, USA
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Genis Calderer
12Center for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
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David van Ijzendoorn
13Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
14Department of Pathology, Stanford University School of Medicine, CA, USA
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Daniel Morgan
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
15Hong Kong University, School of Biomedical Sciences, Honk Kong
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Alessandro Marin
16Expert Analytics AS, Oslo, Norway
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Cho-Yi Chen
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
17Dana-Farber Cancer Institute, Boston, MA, USA
18Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Alex Song
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
19Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA
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Kate Shutta
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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Dawn DeMeo
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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Megha Padi
10Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA
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John Platig
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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Marieke L. Kuijjer
12Center for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway
13Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
20Leiden Center for Computational Oncology, Leiden University, Leiden, The Netherlands
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Kimberly Glass
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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John Quackenbush
1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
3Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
17Dana-Farber Cancer Institute, Boston, MA, USA
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  • For correspondence: johnq@hsph.harvard.edu
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Abstract

Inference and analysis of cellular biological networks requires software tools that integrate multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is an open-source software suite to model biological networks, including context-specific gene regulatory networks and multi-omics partial correlation networks, to conduct differential analyses, estimate community structure, and model the transitions between biological states. The netZoo builds on our ongoing development of network methods, harmonizing the implementations in various computing languages (R, Python, MATLAB, and C) and between methods to allow a better integration of these tools into analytical pipelines. To demonstrate the value of this integrated toolkit, we analyzed the multi-omic data from the Cancer Cell Line Encyclopedia (CCLE) by inferring gene regulatory networks for each cancer cell line and associating network features with other phenotypic attributes such as drug sensitivity. This allowed us to identify transcription factors that play a critical role in both drug resistance and cancer development in melanoma. We also used netZoo to build a pan-cancer, multi-tiered CCLE map and used it to identify known metabolic hallmarks of cancer and to estimate novel context-specific elements that mediate post-transcriptional regulation. Because the netZoo tools are open-source and there is a growing community of both users and developers, we built an ecosystem to support community contributions, share use cases, and visualize networks online. As additional data types become available and our suite of methods grows, we will expand 'the zoo' to incorporate an increasingly sophisticated collection of tools for network inference and analysis.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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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The Network Zoo: a multilingual package for the inference and analysis of biological networks
Marouen Ben Guebila, Tian Wang, Camila M. Lopes-Ramos, Viola Fanfani, Deborah Weighill, Rebekka Burkholz, Daniel Schlauch, Joseph N. Paulson, Michael Altenbuchinger, Abhijeet Sonanwane, James Lim, Genis Calderer, David van Ijzendoorn, Daniel Morgan, Alessandro Marin, Cho-Yi Chen, Alex Song, Kate Shutta, Dawn DeMeo, Megha Padi, John Platig, Marieke L. Kuijjer, Kimberly Glass, John Quackenbush
bioRxiv 2022.05.30.494077; doi: https://doi.org/10.1101/2022.05.30.494077
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The Network Zoo: a multilingual package for the inference and analysis of biological networks
Marouen Ben Guebila, Tian Wang, Camila M. Lopes-Ramos, Viola Fanfani, Deborah Weighill, Rebekka Burkholz, Daniel Schlauch, Joseph N. Paulson, Michael Altenbuchinger, Abhijeet Sonanwane, James Lim, Genis Calderer, David van Ijzendoorn, Daniel Morgan, Alessandro Marin, Cho-Yi Chen, Alex Song, Kate Shutta, Dawn DeMeo, Megha Padi, John Platig, Marieke L. Kuijjer, Kimberly Glass, John Quackenbush
bioRxiv 2022.05.30.494077; doi: https://doi.org/10.1101/2022.05.30.494077

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