A reference map of the human protein interactome
A reference map of the human protein interactome
Abstract Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence 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.
Spirohn Kerstin、Teeking Bridget、Kim Dae-Kyum、Ennajdaoui Hanane、Kassa Yoseph、Hill David E.、Hardy Madeleine F.、Pons Carles、Schlabach Sadie、Babor Mariana、Balcha Dawit、Chin Suet-Feung、Colabella Claudia、De Ridder David、Goehring Liana、Hatchi Elodie、Li Roujia、Rangarajan Sudharshan、Rasla John、Rolland Thomas、San-Miguel Adriana、Shen Yun、Sheykhkarimli Dayag、Sheynkman Gloria M.、Simonovsky Eyal、Twizere Jean-Claude、Weatheritt Robert J.、Yang Xinping、Aloy Patrick、Tavernier Jan、Vidal Marc、Calderwood Michael A.、Roth Frederick P.、Luck Katja、Charloteaux Benoit、Cote Atina G.、Choi Soon Gang、Lemmens Irma、Xia Yu、Landini Serena、Pollis Carl、Jacob Yves、Campos-Laborie Francisco J.、Daley Meaghan、Bader Gary D.、Kov¨￠cs Istv¨￠n A.、Markey Dylan、MacWilliams Andrew、Gaudet Suzanne、Coppin Georges、Haddad Ghazal、Ta?an Murat、Zhong Quan、Yeger-Lotem Esti、Desbuleux Alice、Cafarelli Tiziana、Rayhan Ashyad、Mellor Joseph C.、Dricot Am¨|lie、Basha Omer、Gebbia Marinella、Paulson Joseph N.、Hao Tong、Kishore Nishka、Bowman-Colin Christian、van Lieshout Natascha、Goebels Florian、De Las Rivas Javier、Rak Janusz、Mee Miles W.、Deimling Steven、Bian Wenting、Choi Dongsic、Duran-Frigola Miquel、D?ˉAmata Cassandra、Knapp Jennifer J.、Helmy Mohamed、Weile Jochen、De Rouck Steffi、Tropepe Vincent、Yadav Anupama、Gopal Anjali、Lambourne Luke、Tejeda Alexander、Brignall Ruth、Richardson Aaron D.、Begg Bridget E.、Wang Yang
Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and TechnologyCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCRUK Cambridge Institute, University of CambridgeDepartment of Pharmaceutical Sciences, University of Perugia||Istituto Zooprofilattico Sperimentale dell?ˉUmbria e delle Marche ?°Togo Rosati?±Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev||National Institute for Biotechnology in the Negev, Ben-Gurion University of the NegevMolecular Biology of Diseases, Groupe Interdisciplinaire de G¨|nomique Appliqu¨|e (GIGA) and Laboratory of Viral Interactomes, University of Li¨¨geThe Donnelly Centre, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology||Instituci¨? Catalana de Recerca i Estudis Avan?ats (ICREA)Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB)||Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent UniversityCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical SchoolCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital||Department of Computer Science, University of Toronto||Canadian Institute for Advanced Research (CIFAR)Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB)||Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent UniversityCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Bioengineering, McGill UniversityDepartment of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteD¨|partement de Virologie, Unit¨| de G¨|n¨|tique Mol¨|culaire des Virus ¨¤ ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS)||Universit¨| Paris DiderotCancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Cient¨aficas (CSIC) and University of Salamanca (USAL)||Institute for Biomedical Research of Salamanca (IBSAL)Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteThe Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Department of Computer Science, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Network Science Institute, Northeastern University||Wigner Research Centre for Physics, Institute for Solid State Physics and OpticsCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer Institute||Molecular Biology of Diseases, Groupe Interdisciplinaire de G¨|nomique Appliqu¨|e (GIGA) and Laboratory of Viral Interactomes, University of Li¨¨geCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital||Department of Computer Science, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer Institute||Department of Biological Sciences, Wright State UniversityDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev||National Institute for Biotechnology in the Negev, Ben-Gurion University of the NegevCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer Institute||Molecular Biology of Diseases, Groupe Interdisciplinaire de G¨|nomique Appliqu¨|e (GIGA) and Laboratory of Viral Interactomes, University of Li¨¨geCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital||seqWell, IncCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev||National Institute for Biotechnology in the Negev, Ben-Gurion University of the NegevCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute||Department of Biostatistics, Harvard School of Public Health||Department of Biostatistics, Product Development, Genentech IncCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalDepartment of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalThe Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Department of Computer Science, University of TorontoCancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Cient¨aficas (CSIC) and University of Salamanca (USAL)||Institute for Biomedical Research of Salamanca (IBSAL)The Research Institute of the McGill University Health CentreThe Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Department of Computer Science, University of TorontoDepartment of Cell and Systems Biology, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteThe Research Institute of the McGill University Health CentreInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and TechnologyDepartment of Cell and Systems Biology, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalThe Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Department of Computer Science, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital||Department of Computer Science, University of TorontoCenter for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB)||Cytokine Receptor Laboratory (CRL), Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent UniversityDepartment of Cell and Systems Biology, University of TorontoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||The Donnelly Centre, University of Toronto||Department of Molecular Genetics, University of Toronto||Lunenfeld Tanenbaum Research Institute, Mount Sinai HospitalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer InstituteCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute||Department of Genetics, Blavatnik Institute, Harvard Medical School||Department of Cancer Biology, Dana-Farber Cancer Institute
生物科学研究方法、生物科学研究技术基础医学分子生物学
Spirohn Kerstin,Teeking Bridget,Kim Dae-Kyum,Ennajdaoui Hanane,Kassa Yoseph,Hill David E.,Hardy Madeleine F.,Pons Carles,Schlabach Sadie,Babor Mariana,Balcha Dawit,Chin Suet-Feung,Colabella Claudia,De Ridder David,Goehring Liana,Hatchi Elodie,Li Roujia,Rangarajan Sudharshan,Rasla John,Rolland Thomas,San-Miguel Adriana,Shen Yun,Sheykhkarimli Dayag,Sheynkman Gloria M.,Simonovsky Eyal,Twizere Jean-Claude,Weatheritt Robert J.,Yang Xinping,Aloy Patrick,Tavernier Jan,Vidal Marc,Calderwood Michael A.,Roth Frederick P.,Luck Katja,Charloteaux Benoit,Cote Atina G.,Choi Soon Gang,Lemmens Irma,Xia Yu,Landini Serena,Pollis Carl,Jacob Yves,Campos-Laborie Francisco J.,Daley Meaghan,Bader Gary D.,Kov¨￠cs Istv¨￠n A.,Markey Dylan,MacWilliams Andrew,Gaudet Suzanne,Coppin Georges,Haddad Ghazal,Ta?an Murat,Zhong Quan,Yeger-Lotem Esti,Desbuleux Alice,Cafarelli Tiziana,Rayhan Ashyad,Mellor Joseph C.,Dricot Am¨|lie,Basha Omer,Gebbia Marinella,Paulson Joseph N.,Hao Tong,Kishore Nishka,Bowman-Colin Christian,van Lieshout Natascha,Goebels Florian,De Las Rivas Javier,Rak Janusz,Mee Miles W.,Deimling Steven,Bian Wenting,Choi Dongsic,Duran-Frigola Miquel,D?ˉAmata Cassandra,Knapp Jennifer J.,Helmy Mohamed,Weile Jochen,De Rouck Steffi,Tropepe Vincent,Yadav Anupama,Gopal Anjali,Lambourne Luke,Tejeda Alexander,Brignall Ruth,Richardson Aaron D.,Begg Bridget E.,Wang Yang.A reference map of the human protein interactome[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/605451.点此复制
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