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1. A reference map of the human binary protein interactome.

Author

Katja Luck, Dae-Kyum Kim, Luke Lambourne, Kerstin Spirohn, Bridget E. Begg, Wenting Bian, Ruth Brignall, Tiziana Cafarelli, Francisco J. Campos-Laborie, Benoît Charloteaux, Dong-Sic Choi, Atina G. Coté, Meaghan Daley, Steven Deimling, Alice Desbuleux, Amélie Dricot, Marinella Gebbia, Madeleine F. Hardy, Nishka Kishore, Jennifer J. Knapp, István A. Kovács, Irma Lemmens, Miles W. Mee, Joseph C. Mellor, Carl Pollis, Carles Pons, Aaron D. Richardson, Sadie Schlabach, Bridget Teeking, Anupama Yadav, Mariana Babor, Dawit Balcha, Omer Basha, Christian Bowman-Colin, Suet-Feung Chin, Soon-gang Choi, Claudia Colabella, Georges Coppin, Cassandra D'Amata, David De Ridder, Steffi De Rouck, Miquel Duran-Frigola, Hanane Ennajdaoui, Florian Goebels, Liana Goehring, Anjali Gopal, Ghazal Haddad, Elodie Hatchi, Mohamed Helmy, Yves Jacob, Yoseph Kassa, Serena Landini, Roujia Li, Natascha van Lieshout, Andrew MacWilliams, Dylan Markey, Joseph N. Paulson, Sudharshan Rangarajan, John Rasla, Ashyad Rayhan, Thomas Rolland, Adriana San-Miguel, Yun Shen, Dayag Sheykhkarimli, Gloria M. Sheynkman, Eyal Simonovsky, Murat Tasan, Alexander Tejeda, Vincent Tropepe, Jean-Claude Twizere, Yang Wang 0081, Robert J. Weatheritt, Jochen Weile, Yu Xia 0002, Xinping Yang, Esti Yeger Lotem, Quan Zhong, Patrick Aloy, Gary D. Bader, Javier De Las Rivas, Suzanne Gaudet, Tong Hao, Janusz Rak, Jan Tavernier, David E. Hill, Marc Vidal, Frederick P. Roth, and Michael A. Calderwood

Published
2020
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2. A reference map of the human binary protein interactome

Author

Eyal Simonovsky, Joseph C. Mellor, Amélie Dricot, Marc Vidal, Liana Goehring, Miquel Duran-Frigola, Florian Goebels, Dayag Sheykhkarimli, Thomas Rolland, Murat Tasan, John Rasla, Steffi De Rouck, Carles Pons, Sadie Schlabach, Yoseph Kassa, Claudia Colabella, Dong-Sic Choi, Yves Jacob, Joseph N. Paulson, Javier De Las Rivas, Madeleine F. Hardy, Francisco J. Campos-Laborie, Xinping Yang, Soon Gang Choi, Frederick P. Roth, Kerstin Spirohn, Nishka Kishore, Luke Lambourne, Cassandra D’Amata, Dawit Balcha, Adriana San-Miguel, Anupama Yadav, Anjali Gopal, Suet-Feung Chin, Suzanne Gaudet, Yang Wang, István Kovács, Elodie Hatchi, Natascha van Lieshout, Michael A. Calderwood, Yu Xia, Gloria M. Sheynkman, Robert J. Weatheritt, Marinella Gebbia, Atina G. Cote, Bridget E. Begg, Mohamed Helmy, Katja Luck, Bridget Teeking, Quan Zhong, Serena Landini, David E. Hill, Sudharshan Rangarajan, Georges Coppin, Ghazal Haddad, Omer Basha, Carl Pollis, Dylan Markey, Alice Desbuleux, Hanane Ennajdaoui, Dae-Kyum Kim, Vincent Tropepe, Roujia Li, Steven Deimling, Jennifer J. Knapp, Jan Tavernier, Mariana Babor, Benoit Charloteaux, Gary D. Bader, Alexander O. Tejeda, Aaron Richardson, Ruth Brignall, Ashyad Rayhan, Irma Lemmens, Tong Hao, Christian Bowman-Colin, Janusz Rak, David De Ridder, Jochen Weile, Wenting Bian, Jean-Claude Twizere, Patrick Aloy, Esti Yeger-Lotem, Meaghan Daley, Tiziana M. Cafarelli, Andrew MacWilliams, Miles W. Mee, Yun Shen, National Institutes of Health (US), National Human Genome Research Institute (US), Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fonds de la Recherche Scientifique (Fédération Wallonie-Bruxelles), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Toronto, Mount Sinai Health System, Canadian Institute for Advanced Research (CIFAR), and This work was primarily supported by the National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) grant U41HG001715 (M.V., F.P.R., D.E.H., M.A.C., G.D.B. and J.T.) with additional support from NIH grants P50HG004233 (M.V. and F.P.R.), U01HL098166 (M.V.), U01HG007690 (M.V.), R01GM109199 (M.A.C.), Canadian Institute for Health Research (CIHR) Foundation Grants (F.P.R. and J. Rak), the Canada Excellence Research Chairs Program (F.P.R.) and an American Heart Association grant 15CVGPS23430000 (M.V.). D.-K.K. was supported by a Banting Postdoctoral Fellowship through the Natural Sciences and Engineering Research Council (NSERC) of Canada and by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A6A3A03004385). C. Pons was supported by a Ramon Cajal fellowship (RYC-2017-22959). G.M.S. was supported by NIH Training Grant T32CA009361. M.V. is a Chercheur Qualifié Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium).

Subjects
0301 basic medicine, Multidisciplinary, Proteome, [SDV]Life Sciences [q-bio], Computational biology, Biology, Genome, Phenotype, Interactome, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Article, Protein–protein interaction, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Organ Specificity, Protein Interaction Mapping, Reference map, Humans, Cellular organization, Extracellular Space, 030217 neurology & neurosurgery, Function (biology)
Abstract

et al., Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype–phenotype relationships1,2. 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., This work was primarily supported by the National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) grant U41HG001715 (M.V., F.P.R., D.E.H., M.A.C., G.D.B. and J.T.) with additional support from NIH grants P50HG004233 (M.V. and F.P.R.), U01HL098166 (M.V.), U01HG007690 (M.V.), R01GM109199 (M.A.C.), Canadian Institute for Health Research (CIHR) Foundation Grants (F.P.R. and J. Rak), the Canada Excellence Research Chairs Program (F.P.R.) and an American Heart Association grant 15CVGPS23430000 (M.V.). D.-K.K. was supported by a Banting Postdoctoral Fellowship through the Natural Sciences and Engineering Research Council (NSERC) of Canada and by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A6A3A03004385). C. Pons was supported by a Ramon Cajal fellowship (RYC-2017-22959). G.M.S. was supported by NIH Training Grant T32CA009361. M.V. is a Chercheurv Qualifié Honoraire from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium).

Published
2020
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3. A reference map of the human protein interactome

Author

Madeleine F. Hardy, Bridget Teeking, Francisco J. Campos-Laborie, Dayag Sheykhkarimli, Dawit Balcha, Anjali Gopal, Marinella Gebbia, Ashyad Rayhan, Carles Pons, Gloria M. Sheynkman, Yves Jacob, Suzanne Gaudet, Aaron Richardson, Yoseph Kassa, Elodie Hatchi, Kerstin Spirohn, Dong-Sic Choi, Yu Xia, Eyal Simonovsky, David E. Hill, Hanane Ennajdaoui, Steven Deimling, Joseph N. Paulson, Natascha van Lieshout, Vincent Tropepe, Michael A. Calderwood, István Kovács, Gary D. Bader, Luke Lambourne, Sudharshan Rangarajan, Tiziana M. Cafarelli, Carl Pollis, Suet-Feung Chin, Alice Desbuleux, Andrew MacWilliams, Amélie Dricot, Jean-Claude Twizere, Patrick Aloy, Atina G. Cote, Marc Vidal, Jan Tavernier, Javier De Las Rivas, Cassandra D’Amata, Alexander O. Tejeda, Esti Yeger-Lotem, Liana Goehring, Joseph C. Mellor, Meaghan Daley, Irma Lemmens, Soon Gang Choi, Christian Bowman-Colin, Ghazal Haddad, Janusz Rak, Florian Goebels, Robert J. Weatheritt, Mariana Babor, Yang Wang, Thomas Rolland, Steffi De Rouck, Jochen Weile, Serena Landini, John Rasla, Sadie Schlabach, Nishka Kishore, Bridget E. Begg, Ruth Brignall, Quan Zhong, Tong Hao, David De Ridder, Claudia Colabella, Frederick P. Roth, Anupama Yadav, Mohamed Helmy, Katja Luck, Omer Basha, Dae-Kyum Kim, Benoit Charloteaux, Georges Coppin, Dylan Markey, Roujia Li, Miquel Duran-Frigola, Adriana San-Miguel, Wenting Bian, Miles W. Mee, Jennifer J. Knapp, Yun Shen, Murat Tasan, Xinping Yang, Dana-Farber Cancer Institute [Boston], Division of Medical Physics in Radiology [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Cancer Research UK Cambridge Institute (CRUK), University of Cambridge [UK] (CAM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Harvard Medical School [Boston] (HMS), University of Toronto, Universidad de Salamanca, McGill University Health Center [Montreal] (MUHC), Mount Sinai Hospital [Toronto, Canada] (MSH), Université de Liège, Wigner Research Centre for Physics [Budapest], Hungarian Academy of Sciences (MTA), Northeastern University [Boston], Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University [Belgium] (UGENT), Barcelona Institute of Science and Technology (BIST), Ben-Gurion University of the Negev (BGU), Università degli Studi di Perugia (UNIPG), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Canadian Institute for Advanced Research (CIFAR), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Perugia = University of Perugia (UNIPG), and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Context (language use), Computational biology, Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Genome, Interactome, Human genetics, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Human interactome, Proteome, 030217 neurology & neurosurgery, Function (biology), 030304 developmental biology
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.

Published
2019
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