A reference map of the human binary protein interactome

Katja Luck; Dae Kyum Kim; Luke Lambourne; Kerstin Spirohn; Bridget E. Begg; Wenting Bian; Ruth Brignall; Tiziana Cafarelli; Francisco J. Campos-Laborie; Benoit Charloteaux; Dongsic 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 Taşan; Alexander Tejeda; Vincent Tropepe; Jean Claude Twizere; Yang Wang; Robert J. Weatheritt; Jochen Weile; Yu Xia; 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; Michael A. Calderwood

doi:10.1038/s41586-020-2188-x

A reference map of the human binary protein interactome

Katja Luck, Dae Kyum Kim, Luke Lambourne, Kerstin Spirohn, Bridget E. Begg, Wenting Bian, Ruth Brignall, Tiziana Cafarelli, Francisco J. Campos-Laborie, Benoit Charloteaux, Dongsic Choi, Atina G. Coté, Meaghan Daley, Steven Deimling, Alice Desbuleux, Amélie Dricot, Marinella Gebbia, Madeleine F. Hardy, Nishka Kishore, Jennifer J. KnappIstván 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 Taşan, Alexander Tejeda, Vincent Tropepe, Jean Claude Twizere, Yang Wang, Robert J. Weatheritt, Jochen Weile, Yu Xia, 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, Michael A. Calderwood

^*Corresponding author for this work

Physics and Astronomy

Research output: Contribution to journal › Article › peer-review

770 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	402-408
Number of pages	7
Journal	Nature
Volume	580
Issue number	7803
DOIs	https://doi.org/10.1038/s41586-020-2188-x
State	Published - Apr 16 2020

Funding

Acknowledgements The authors gratefully acknowledge, in memoriam, support and insight from D. Allinger. We thank P. Porras Millan and the IntAct team for their help in disseminating our PPI data via IntAct, before and after publication. We thank U. Braunschweig, J. Ellis and B. J. Blencowe for help with data analysis. We also thank Q. Zhu, O. G. Troyanskaya, J. Pan and C. Kadoch for sharing co-expression and co-fitness data, respectively. We thank K. S. Tuttle for help with graphics. 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).

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Luck, K., Kim, D. K., Lambourne, L., Spirohn, K., Begg, B. E., Bian, W., Brignall, R., Cafarelli, T., Campos-Laborie, F. J., Charloteaux, B., Choi, D., Coté, A. G., Daley, M., Deimling, S., Desbuleux, A., Dricot, A., Gebbia, M., Hardy, M. F., Kishore, N., ... Calderwood, M. A. (2020). A reference map of the human binary protein interactome. Nature, 580(7803), 402-408. https://doi.org/10.1038/s41586-020-2188-x

@article{c8e04dae4afe4f73ab308f30d9139ad7,

title = "A reference map of the human binary protein interactome",

abstract = "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 {\textquoteleft}all-by-all{\textquoteright} reference interactome map of human binary protein interactions, or {\textquoteleft}HuRI{\textquoteright}. 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.",

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

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = apr,

day = "16",

doi = "10.1038/s41586-020-2188-x",

language = "English (US)",

volume = "580",

pages = "402--408",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7803",

}

Luck, K, Kim, DK, Lambourne, L, Spirohn, K, Begg, BE, Bian, W, Brignall, R, Cafarelli, T, Campos-Laborie, FJ, Charloteaux, B, Choi, D, Coté, AG, Daley, M, Deimling, S, Desbuleux, A, Dricot, A, Gebbia, M, Hardy, MF, Kishore, N, Knapp, JJ, Kovács, IA, Lemmens, I, Mee, MW, Mellor, JC, Pollis, C, Pons, C, Richardson, AD, Schlabach, S, Teeking, B, Yadav, A, Babor, M, Balcha, D, Basha, O, Bowman-Colin, C, Chin, SF, Choi, SG, Colabella, C, Coppin, G, D’Amata, C, De Ridder, D, De Rouck, S, Duran-Frigola, M, Ennajdaoui, H, Goebels, F, Goehring, L, Gopal, A, Haddad, G, Hatchi, E, Helmy, M, Jacob, Y, Kassa, Y, Landini, S, Li, R, van Lieshout, N, MacWilliams, A, Markey, D, Paulson, JN, Rangarajan, S, Rasla, J, Rayhan, A, Rolland, T, San-Miguel, A, Shen, Y, Sheykhkarimli, D, Sheynkman, GM, Simonovsky, E, Taşan, M, Tejeda, A, Tropepe, V, Twizere, JC, Wang, Y, Weatheritt, RJ, Weile, J, Xia, Y, Yang, X, Yeger-Lotem, E, Zhong, Q, Aloy, P, Bader, GD, De Las Rivas, J, Gaudet, S, Hao, T, Rak, J, Tavernier, J, Hill, DE, Vidal, M, Roth, FP & Calderwood, MA 2020, 'A reference map of the human binary protein interactome', Nature, vol. 580, no. 7803, pp. 402-408. https://doi.org/10.1038/s41586-020-2188-x

TY - JOUR

T1 - A reference map of the human binary protein interactome

AU - Luck, Katja

AU - Kim, Dae Kyum

AU - Lambourne, Luke

AU - Spirohn, Kerstin

AU - Begg, Bridget E.

AU - Bian, Wenting

AU - Brignall, Ruth

AU - Cafarelli, Tiziana

AU - Campos-Laborie, Francisco J.

AU - Charloteaux, Benoit

AU - Choi, Dongsic

AU - Coté, Atina G.

AU - Daley, Meaghan

AU - Deimling, Steven

AU - Desbuleux, Alice

AU - Dricot, Amélie

AU - Gebbia, Marinella

AU - Hardy, Madeleine F.

AU - Kishore, Nishka

AU - Knapp, Jennifer J.

AU - Kovács, István A.

AU - Lemmens, Irma

AU - Mee, Miles W.

AU - Mellor, Joseph C.

AU - Pollis, Carl

AU - Pons, Carles

AU - Richardson, Aaron D.

AU - Schlabach, Sadie

AU - Teeking, Bridget

AU - Yadav, Anupama

AU - Babor, Mariana

AU - Balcha, Dawit

AU - Basha, Omer

AU - Bowman-Colin, Christian

AU - Chin, Suet Feung

AU - Choi, Soon Gang

AU - Colabella, Claudia

AU - Coppin, Georges

AU - D’Amata, Cassandra

AU - De Ridder, David

AU - De Rouck, Steffi

AU - Duran-Frigola, Miquel

AU - Ennajdaoui, Hanane

AU - Goebels, Florian

AU - Goehring, Liana

AU - Gopal, Anjali

AU - Haddad, Ghazal

AU - Hatchi, Elodie

AU - Helmy, Mohamed

AU - Jacob, Yves

AU - Kassa, Yoseph

AU - Landini, Serena

AU - Li, Roujia

AU - van Lieshout, Natascha

AU - MacWilliams, Andrew

AU - Markey, Dylan

AU - Paulson, Joseph N.

AU - Rangarajan, Sudharshan

AU - Rasla, John

AU - Rayhan, Ashyad

AU - Rolland, Thomas

AU - San-Miguel, Adriana

AU - Shen, Yun

AU - Sheykhkarimli, Dayag

AU - Sheynkman, Gloria M.

AU - Simonovsky, Eyal

AU - Taşan, Murat

AU - Tejeda, Alexander

AU - Tropepe, Vincent

AU - Twizere, Jean Claude

AU - Wang, Yang

AU - Weatheritt, Robert J.

AU - Weile, Jochen

AU - Xia, Yu

AU - Yang, Xinping

AU - Yeger-Lotem, Esti

AU - Zhong, Quan

AU - Aloy, Patrick

AU - Bader, Gary D.

AU - De Las Rivas, Javier

AU - Gaudet, Suzanne

AU - Hao, Tong

AU - Rak, Janusz

AU - Tavernier, Jan

AU - Hill, David E.

AU - Vidal, Marc

AU - Roth, Frederick P.

AU - Calderwood, Michael A.

PY - 2020/4/16

Y1 - 2020/4/16

N2 - 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.

AB - 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.

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U2 - 10.1038/s41586-020-2188-x

DO - 10.1038/s41586-020-2188-x

M3 - Article

C2 - 32296183

AN - SCOPUS:85083046188

SN - 0028-0836

VL - 580

SP - 402

EP - 408

JO - Nature

JF - Nature

IS - 7803

ER -

A reference map of the human binary protein interactome

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