A reference map of the human binary protein interactome.

Nature. 2020 Apr;580(7803):402-408. Epub 2020 Apr 08

Katja Luck ¹ , Dae-Kyum Kim ² , Luke Lambourne ¹ , Kerstin Spirohn ¹ , Bridget E Begg ¹ ,

Katja Luck ¹ , Dae-Kyum Kim ² , Luke Lambourne ¹ , Kerstin Spirohn ¹ , Bridget E Begg ¹ , Wenting Bian ¹ , Ruth Brignall ¹ , Tiziana Cafarelli ¹ , Francisco J Campos-Laborie ³ , Benoit Charloteaux ¹ , Dongsic Choi ⁴ , Atina G Coté ² , Meaghan Daley ¹ , Steven Deimling ⁵ , Alice Desbuleux ⁶ , Amélie Dricot ¹ , Marinella Gebbia ² , Madeleine F Hardy ¹ , Nishka Kishore ² , Jennifer J Knapp ² , István A Kovács ⁷ , Irma Lemmens ⁸ , Miles W Mee ⁹ , Joseph C Mellor ¹⁰ , Carl Pollis ¹ , Carles Pons ¹¹ , Aaron D Richardson ¹ , Sadie Schlabach ¹ , Bridget Teeking ¹ , Anupama Yadav ¹ , Mariana Babor ² , Dawit Balcha ¹ , Omer Basha ¹² , Christian Bowman-Colin ¹ , Suet-Feung Chin ¹³ , Soon Gang Choi ¹ , Claudia Colabella ¹⁴ , Georges Coppin ⁶ , Cassandra D'Amata ⁵ , David De Ridder ¹ , Steffi De Rouck ⁸ , Miquel Duran-Frigola ¹¹ , Hanane Ennajdaoui ² , Florian Goebels ⁹ , Liana Goehring ¹ , Anjali Gopal ² , Ghazal Haddad ² , Elodie Hatchi ¹ , Mohamed Helmy ⁹ , Yves Jacob ¹⁵ , Yoseph Kassa ¹ , Serena Landini ¹ , Roujia Li ² , Natascha van Lieshout ² , Andrew MacWilliams ¹ , Dylan Markey ¹ , Joseph N Paulson ¹⁶ , Sudharshan Rangarajan ¹ , John Rasla ¹ , Ashyad Rayhan ² , Thomas Rolland ¹ , Adriana San-Miguel ¹ , Yun Shen ¹ , Dayag Sheykhkarimli ² , Gloria M Sheynkman ¹ , Eyal Simonovsky ¹² , Murat Taşan ⁹ , Alexander Tejeda ¹ , Vincent Tropepe ⁵ , Jean-Claude Twizere ⁶ , Yang Wang ¹ , Robert J Weatheritt ¹⁷ , Jochen Weile ⁹ , Yu Xia ¹⁸ , Xinping Yang ¹ , Esti Yeger-Lotem ¹² , Quan Zhong ¹⁹ , Patrick Aloy ²⁰ , Gary D Bader ⁹ , Javier De Las Rivas ³ , Suzanne Gaudet ¹ , Tong Hao ¹ , Janusz Rak ⁴ , Jan Tavernier ⁸ , David E Hill ²¹ , Marc Vidal ²² , Frederick P Roth ²³ , Michael A Calderwood ²⁴

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Author information

¹ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Lunenfeld-Tanenbaum Research Institute (LTRI), Sinai Health System, Toronto, Ontario, Canada.
³ Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
⁴ The Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada.
⁵ Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
⁶ Molecular Biology of Diseases, Groupe Interdisciplinaire de Génomique Appliquée (GIGA) and Laboratory of Viral Interactomes, University of Liège, Liège, Belgium.
⁷ Wigner Research Centre for Physics, Institute for Solid State Physics and Optics, Budapest, Hungary.
⁸ Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
⁹ Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
¹⁰ seqWell, Beverly, MA, USA.
¹¹ Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
¹² National Institute for Biotechnology in the Negev (NIBN), Ben-Gurion University of the Negev, Beer-Sheva, Israel.
¹³ Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.
¹⁴ Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche "Togo Rosati" (IZSUM), Perugia, Italy.
¹⁵ Université Paris Diderot, Paris, France.
¹⁶ Department of Biostatistics, Product Development, Genentech Inc., South San Francisco, CA, USA.
¹⁷ The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Department of Bioengineering, McGill University, Montreal, Quebec, Canada.
¹⁹ Department of Biological Sciences, Wright State University, Dayton, OH, USA.
²⁰ Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
²¹ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. david_hill@dfci.harvard.edu.
²² Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. marc_vidal@dfci.harvard.edu.
²³ Canadian Institute for Advanced Research (CIFAR), Toronto, Ontario, Canada. fritz.roth@utoronto.ca.
²⁴ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. michael_calderwood@dfci.harvard.edu.

摘要

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships^1,2. Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome³, transcriptome⁴ and proteome⁵ data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes.

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