한빛사 논문
University of Toronto, Mount Sinai Hospital, Dana-Farber Cancer Institute
Katja Luck1-3,33, Dae-Kyum Kim1,4-6,33, Luke Lambourne1-3,33, Kerstin Spirohn1-3,33, Bridget E. Begg1-3, Wenting Bian1-3, Ruth Brignall1-3, Tiziana Cafarelli1-3, Francisco J. Campos-Laborie7,8, Benoit Charloteaux1-3, Dongsic Choi9, Atina G. Cote1,4-6, Meaghan Daley1-3, Steven Deimling10, Alice Desbuleux1-3,11, Amélie Dricot1-3, Marinella Gebbia1,4-6, Madeleine F. Hardy1-3, Nishka Kishore1,4-6, Jennifer J. Knapp1,4-6, István A. Kovács1,12,13, Irma Lemmens14,15, Miles W. Mee4,5,16, Joseph C. Mellor1,6,17, Carl Pollis1-3, Carles Pons18, Aaron D. Richardson1-3, Sadie Schlabach1-3, Bridget Teeking1-3, Anupama Yadav1-3, Mariana Babor1,4-6, Dawit Balcha1-3, Omer Basha19,20, Suet-Feung Chin21, Soon Gang Choi1-3, Claudia Colabella22,23, Georges Coppin1-3,11, Cassandra D'Amata10, David De Ridder1-3, Steffi De Rouck14,15, Miquel Duran-Frigola18, Hanane Ennajdaoui1,4-6, Florian Goebels4,5,16, Anjali Gopal1,4-6, Ghazal Haddad1,4-6, Mohamed Helmy4,5,16, Yves Jacob24,25, Yoseph Kassa1-3, Roujia Li1,4-6, Natascha van Lieshout1,4-6, Andrew MacWilliams1-3, Dylan Markey1-3, Joseph N. Paulson26-28, Sudharshan Rangarajan1-3, John Rasla1-3, Ashyad Rayhan1,4-6, Thomas Rolland1-3, Adriana San Miguel1-3, Yun Shen1-3, Dayag Sheykhkarimli1,4-6, Gloria M. Sheynkman1-3, Eyal Simonovsky19,20, Murat Taşan1,4-6,16, Alexander Tejeda1-3, Jean-Claude Twizere11, Yang Wang1-3, Robert Weatheritt4, Jochen Weile1,4-6,16, Yu Xia1,3,29, Xinping Yang1-3, Esti Yeger-Lotem19,20, Quan Zhong1-3,30, Patrick Aloy18,31, Gary D. Bader4,5,16, Javier De Las Rivas7,8, Suzanne Gaudet1-3, Tong Hao1-3, Janusz Rak9, Jan Tavernier14,15, Vincent Tropepe10, David E. Hill1-3,*, Marc Vidal1,2,*, Frederick P. Roth1,4-6,16,32,*, & Michael A. Calderwood1-3,*
Authors other than co-first and co-corresponding are listed alphabetically within their group
1Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
2Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. 3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. 4The Donnelly Centre, University of Toronto, Toronto, ON, Canada. 5Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. 6Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. 7Cancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Cientificas (CSIC) and University of Salamanca (USAL), Salamanca, Spain. 8Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain. 9The Research Institute of the McGill University Health Centre, Montreal, QC, Canada. 10Department of Cell & Systems Biology, University of Toronto, Toronto, ON, Canada. 11Molecular Biology of Diseases, Groupe Interdisciplinaire de Génomique Appliquée (GIGA) and Laboratory of Viral Interactomes, University of Liège, Liège, Belgium. 12Network Science Institute, Northeastern University, Boston, MA, USA. 13Wigner Research Centre for Physics, Institute for Solid State Physics and Optics, Budapest, Hungary. 14Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium. 15Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. 16Department of Computer Science, University of Toronto, Toronto, ON, Canada. 17SeqWell Inc, Boston, MA, USA. 18Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain. 19Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 20National Institute
for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 21CRUK
Cambridge Institute, University of Cambridge, Cambridge, UK. 22Department of Pharmaceutical Sciences, University of Perugia, Italy. 23Istituto Zooprofilattico Sperimentale dell’Umbria e delle Marche “Togo Rosati”, Perugia, Italy. 24Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS), Paris, France. 25Université Paris Diderot, Paris, France. 26Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. 27Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA. 28Department of Biostatistics, Product Development, Genentech Inc., South San Francisco, CA, USA. 29Department of Bioengineering, McGill University, Montreal, QC, Canada. 30Department of Biological Sciences, Wright State University, Dayton, OH, USA. 31Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain. 32Canadian Institute for Advanced Research, Toronto, ON, Canada.33These authors contributed equally: Katja Luck, Dae-Kyum Kim, Luke Lambourne, Kerstin Spirohn.
*Correspondence to David E. Hill or Marc Vidal or Frederick P. Roth or Michael A. Calderwood
Abstract
Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence recently revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here, we present the first human “all-by-all” binary reference interactome map, or “HuRI”. With ∼53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.
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