A reference map of the human binary protein interactome,Nature

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A reference map of the human binary protein interactome
Nature ( IF 50.5 ) Pub Date : 2020-04-08 , DOI: 10.1038/s41586-020-2188-x
Katja Luck _{1,

2,

3} , Dae-Kyum Kim _{1,

4,

5,

6} , Luke Lambourne _{1,

2,

3} , Kerstin Spirohn _{1,

2,

3} , Bridget E Begg _{1,

2,

3} , Wenting Bian _{1,

2,

3} , Ruth Brignall _{1,

2,

3} , Tiziana Cafarelli _{1,

2,

3} , Francisco J Campos-Laborie _{7,

8} , Benoit Charloteaux _{1,

2,

3} , Dongsic Choi ₉ , Atina G Coté _{1,

4,

5,

6} , Meaghan Daley _{1,

2,

3} , Steven Deimling ₁₀ , Alice Desbuleux _{1,

2,

3,

11} , Amélie Dricot _{1,

2,

3} , Marinella Gebbia _{1,

4,

5,

6} , Madeleine F Hardy _{1,

2,

3} , Nishka Kishore _{1,

4,

5,

6} , Jennifer J Knapp _{1,

4,

5,

6} , István A Kovács _{1,

12,

13} , Irma Lemmens _{14,

15} , Miles W Mee _{4,

5,

16} , Joseph C Mellor _{1,

4,

5,

6,

17} , Carl Pollis _{1,

2,

3} , Carles Pons ₁₈ , Aaron D Richardson _{1,

2,

3} , Sadie Schlabach _{1,

2,

3} , Bridget Teeking _{1,

2,

3} , Anupama Yadav _{1,

2,

3} , Mariana Babor _{1,

4,

5,

6} , Dawit Balcha _{1,

2,

3} , Omer Basha _{19,

20} , Christian Bowman-Colin _{2,

3} , Suet-Feung Chin ₂₁ , Soon Gang Choi _{1,

2,

3} , Claudia Colabella _{22,

23} , Georges Coppin _{1,

2,

3,

11} , Cassandra D'Amata ₁₀ , David De Ridder _{1,

2,

3} , Steffi De Rouck _{14,

15} , Miquel Duran-Frigola ₁₈ , Hanane Ennajdaoui _{1,

4,

5,

6} , Florian Goebels _{4,

5,

16} , Liana Goehring _{2,

3} , Anjali Gopal _{1,

4,

5,

6} , Ghazal Haddad _{1,

4,

5,

6} , Elodie Hatchi _{2,

3} , Mohamed Helmy _{4,

5,

16} , Yves Jacob _{24,

25} , Yoseph Kassa _{1,

2,

3} , Serena Landini _{2,

3} , Roujia Li _{1,

4,

5,

6} , Natascha van Lieshout _{1,

4,

5,

6} , Andrew MacWilliams _{1,

2,

3} , Dylan Markey _{1,

2,

3} , Joseph N Paulson _{26,

27,

28} , Sudharshan Rangarajan _{1,

2,

3} , John Rasla _{1,

2,

3} , Ashyad Rayhan _{1,

4,

5,

6} , Thomas Rolland _{1,

2,

3} , Adriana San-Miguel _{1,

2,

3} , Yun Shen _{1,

2,

3} , Dayag Sheykhkarimli _{1,

4,

5,

6} , Gloria M Sheynkman _{1,

2,

3} , Eyal Simonovsky _{19,

20} , Murat Taşan _{1,

4,

5,

6,

16} , Alexander Tejeda _{1,

2,

3} , Vincent Tropepe ₁₀ , Jean-Claude Twizere ₁₁ , Yang Wang _{1,

2,

3} , Robert J Weatheritt ₄ , Jochen Weile _{1,

4,

5,

6,

16} , Yu Xia _{1,

29} , Xinping Yang _{1,

2,

3} , Esti Yeger-Lotem _{19,

20} , Quan Zhong _{1,

2,

3,

30} , Patrick Aloy _{18,

31} , Gary D Bader _{4,

5,

16} , Javier De Las Rivas _{7,

8} , Suzanne Gaudet _{1,

2,

3} , Tong Hao _{1,

2,

3} , Janusz Rak ₉ , Jan Tavernier _{14,

15} , David E Hill _{1,

2,

3} , Marc Vidal _{1,

2} , Frederick P Roth _{1,

4,

5,

6,

16,

32} , Michael A Calderwood _{1,

2,

3}

Affiliation

Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute (LTRI), Sinai Health System, Toronto, Ontario, Canada.
Cancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain.
Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
The Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada.
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
Molecular Biology of Diseases, Groupe Interdisciplinaire de Génomique Appliquée (GIGA) and Laboratory of Viral Interactomes, University of Liège, Liège, Belgium.
Network Science Institute, Northeastern University, Boston, MA, USA.
Wigner Research Centre for Physics, Institute for Solid State Physics and Optics, Budapest, Hungary.
Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium.
Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
seqWell, Beverly, MA, USA.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
National Institute for Biotechnology in the Negev (NIBN), Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.
Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche "Togo Rosati" (IZSUM), Perugia, Italy.
Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS), Paris, France.
Université Paris Diderot, Paris, France.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
Department of Biostatistics, Product Development, Genentech Inc., South San Francisco, CA, USA.
Department of Bioengineering, McGill University, Montreal, Quebec, Canada.
Department of Biological Sciences, Wright State University, Dayton, OH, USA.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.
Canadian Institute for Advanced Research (CIFAR), Toronto, Ontario, Canada.

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.

中文翻译：

人类二元蛋白相互作用组的参考图

对细胞组织和基因组功能的全球洞察需要全面了解介导基因型-表型关系^1,2的相互作用组网络。在这里，我们提出了人类二元蛋白质相互作用或“HuRI”的人类“全部”参考相互作用组图。HuRI 有大约 53,000 种蛋白质-蛋白质相互作用，其此类相互作用的数量大约是小规模研究中高质量策划的相互作用的四倍。HuRI与基因组³、转录组⁴和蛋白质组^5的整合数据使细胞功能能够在大多数生理或病理细胞环境中进行研究。我们证明了 HuRI 在识别蛋白质-蛋白质相互作用的特定亚细胞作用方面的效用。推断的组织特异性网络揭示了形成细胞环境特异性功能的一般原则，并阐明了可能构成孟德尔疾病组织特异性表型的潜在分子机制。HuRI 是一个系统的蛋白质组参考，将基因组变异与表型结果联系起来。

更新日期：2020-04-08

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