A reference map of the human binary protein interactome

Katja Luck (1, 2) , Dae-Kyum Kim , Luke Lambourne , Kerstin Spirohn , Bridget Begg , Wenting Bian , Ruth Brignall , Tiziana Cafarelli , Francisco Campos-Laborie , Benoit Charloteaux , Dongsic Choi , Atina Coté , Meaghan Daley , Steven Deimling , Alice Desbuleux , Amélie Dricot , Marinella Gebbia , Madeleine Hardy , Nishka Kishore , Jennifer Knapp , István Kovács , Irma Lemmens , Miles Mee , Joseph Mellor , Carl Pollis , Carles Pons , Aaron 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 (3) , Yoseph Kassa , Serena Landini , Roujia Li , Natascha van Lieshout , Andrew Macwilliams , Dylan Markey , Joseph Paulson , Sudharshan Rangarajan , John Rasla , Ashyad Rayhan , Thomas Rolland , Adriana San-Miguel , Yun Shen , Dayag Sheykhkarimli , Gloria Sheynkman , Eyal Simonovsky , Murat Taşan , Alexander Tejeda , Vincent Tropepe , Jean-Claude Twizere , Yang Wang , Robert Weatheritt , Jochen Weile , Yu Xia , Xinping Yang , Esti Yeger-Lotem , Quan Zhong , Patrick Aloy , Gary Bader , Javier de las Rivas , Suzanne Gaudet , Tong Hao , Janusz Rak , Jan Tavernier , David Hill (1, 2) , Marc Vidal (1, 2) , Frederick Roth (1, 4, 5, 6) , Michael Calderwood (1, 2)

1 Dana-Farber Cancer Institute [Boston]
2 HMS - Harvard Medical School [Boston]
3 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
4 University of Toronto
5 Mount Sinai Health System
6 CIFAR - Canadian Institute for Advanced Research

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.

Domains: Life Sciences [q-bio]

Katja Luck, Dae-Kyum Kim, Luke Lambourne, Kerstin Spirohn, Bridget Begg, et al.. A reference map of the human binary protein interactome. Nature, 2020, 580 (7803), pp.402-408. ⟨10.1038/s41586-020-2188-x⟩. ⟨pasteur-04098559⟩