A reference map of the human binary protein interactome.

[en] 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 genome(3), transcriptome(4) and proteome(5) 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Luck, Katja

Kim, Dae-Kyum

Lambourne, Luke

Spirohn, Kerstin

Begg, Bridget E.

Bian, Wenting

Brignall, Ruth

Cafarelli, Tiziana

Campos-Laborie, Francisco J.

CHARLOTEAUX, Benoit ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique

More authors (78 more)

Language :

English

Title :

A reference map of the human binary protein interactome.

Publication date :

2020

Journal title :

Nature

ISSN :

0028-0836

eISSN :

1476-4687

Publisher :

Nature Publishing Group, London, United Kingdom

Volume :

580

Issue :

7803

Pages :

402-408

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 22 November 2021

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241 (2 by ULiège)

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Scopus citations^®

566

Scopus citations^®
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536

OpenCitations

471

Bibliography

Vidal, M., Cusick, M. E. & Barabási, A.-L. Interactome networks and human disease. Cell 144, 986–998 (2011).
Rolland, T. et al. A proteome-scale map of the human interactome network. Cell 159, 1212–1226 (2014).
Amberger, J. S., Bocchini, C. A., Schiettecatte, F., Scott, A. F. & Hamosh, A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 43, D789–D798 (2015).
Melé, M. et al. The human transcriptome across tissues and individuals. Science 348, 660–665 (2015).
Thul, P. J. et al. A subcellular map of the human proteome. Science 356, eaal3321 (2017).
Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016).
The FANTOM Consortium and the RIKEN PMI and CLST (DGT). A promoter-level mammalian expression atlas. Nature 507, 462–470 (2014).
Regev, A. et al. The human cell atlas. eLife 6, e27041 (2017).
Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).
Venter, J. C. et al. The sequence of the human genome. Science 291, 1304–1351 (2001).
Wan, C. et al. Panorama of ancient metazoan macromolecular complexes. Nature 525, 339–344 (2015).
Hein, M. Y. et al. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 163, 712–723 (2015).
Huttlin, E. L. et al. Architecture of the human interactome defines protein communities and disease networks. Nature 545, 505–509 (2017).
Rual, J.-F. et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173–1178 (2005).
Braun, P. et al. An experimentally derived confidence score for binary protein-protein interactions. Nat. Methods 6, 91–97 (2009).
Venkatesan, K. et al. An empirical framework for binary interactome mapping. Nat. Methods 6, 83–90 (2009).
Chen, Y.-C., Rajagopala, S. V., Stellberger, T. & Uetz, P. Exhaustive benchmarking of the yeast two-hybrid system. Nat. Methods 7, 667–668 (2010).
Choi, S. G. et al. Maximizing binary interactome mapping with a minimal number of assays. Nat. Commun. 10, 3907 (2019).
Eyckerman, S. et al. Design and application of a cytokine-receptor-based interaction trap. Nat. Cell Biol. 3, 1114–1119 (2001).
Cassonnet, P. et al. Benchmarking a luciferase complementation assay for detecting protein complexes. Nat. Methods 8, 990–992 (2011).
Mosca, R., Céol, A. & Aloy, P. Interactome3D: adding structural details to protein networks. Nat. Methods 10, 47–53 (2013).
Tompa, P., Davey, N. E., Gibson, T. J. & Babu, M. M. A million peptide motifs for the molecular biologist. Mol. Cell 55, 161–169 (2014).
Sambourg, L. & Thierry-Mieg, N. New insights into protein-protein interaction data lead to increased estimates of the S. cerevisiae interactome size. BMC Bioinformatics 11, 605 (2010).
Leid, M. et al. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 68, 377–395 (1992).
Willy, P. J. et al. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 9, 1033–1045 (1995).
Kovács, I. A. et al. Network-based prediction of protein interactions. Nat. Commun. 10, 1240 (2019).
Baryshnikova, A. Systematic functional annotation and visualization of biological networks. Cell Syst. 2, 412–421 (2016).
Graham, D. B. et al. TMEM258 is a component of the oligosaccharyltransferase complex controlling ER stress and intestinal inflammation. Cell Rep. 17, 2955–2965 (2016).
Yamamoto, Y., Yoshida, A., Miyazaki, N., Iwasaki, K. & Sakisaka, T. Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-like fashion. Biochem. J. 458, 69–79 (2014).
Abdel-Salam, G. M. H. et al. A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS). Am. J. Med. Genet. A. 158A, 2788–2796 (2012).
Jeong, H., Mason, S. P., Barabási, A.-L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001).
Capra, J. A., Williams, A. G. & Pollard, K. S. ProteinHistorian: tools for the comparative analysis of eukaryote protein origin. PLOS Comput. Biol. 8, e1002567 (2012).
Pan, J. et al. Interrogation of mammalian protein complex structure, function, and membership using genome-scale fitness screens. Cell Syst. 6, 555–568 (2018).
Yu, H. et al. High-quality binary protein interaction map of the yeast interactome network. Science 322, 104–110 (2008).
Kim, D. K. et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics 31, 933–939 (2015).
Hessvik, N. P. & Llorente, A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci. 75, 193–208 (2018).
Imjeti, N. S. et al. Syntenin mediates SRC function in exosomal cell-to-cell communication. Proc. Natl Acad. Sci. USA 114, 12495–12500 (2017).
Calderone, A., Castagnoli, L. & Cesareni, G. mentha: a resource for browsing integrated protein-interaction networks. Nat. Methods 10, 690–691 (2013).
Kiran, M. & Nagarajaram, H. A. Global versus local hubs in human protein-protein interaction network. J. Proteome Res. 12, 5436–5446 (2013).
Yang, L. et al. Comparative analysis of housekeeping and tissue-selective genes in human based on network topologies and biological properties. Mol. Genet. Genomics 291, 1227–1241 (2016).
Paulson, J. N. et al. Tissue-aware RNA-Seq processing and normalization for heterogeneous and sparse data. BMC Bioinformatics 18, 437 (2017).
Bossi, A. & Lehner, B. Tissue specificity and the human protein interaction network. Mol. Syst. Biol. 5, 260 (2009).
Barshir, R., Shwartz, O., Smoly, I. Y. & Yeger-Lotem, E. Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases. PLOS Comput. Biol. 10, e1003632 (2014).
Sahni, N. et al. Widespread macromolecular interaction perturbations in human genetic disorders. Cell 161, 647–660 (2015).
Reynolds, J. J., Walker, A. K., Gilmore, E. C., Walsh, C. A. & Caldecott, K. W. Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. Nucleic Acids Res. 40, 6608–6619 (2012).
Landrum, M. J. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46 (D1), D1062–D1067 (2018).
Bhatnagar, S. et al. TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein. Nature 516, 116–120 (2014).
Olivé, M. et al. New cardiac and skeletal protein aggregate myopathy associated with combined MuRF1 and MuRF3 mutations. Hum. Mol. Genet. 24, 3638–3650 (2015).
Novarino, G. et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343, 506–511 (2014).
Yang, X. et al. Widespread expansion of protein interaction capabilities by alternative splicing. Cell 164, 805–817 (2016).