A reference map of the human protein interactome

Author:

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

Abstract

AbstractGlobal 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.

Publisher

Cold Spring Harbor Laboratory

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