OpenLB
Open Library of Bioscience
Advanced Search
Nature
04, 2020;580 (7803): 402-408.

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
Author Information
  1. Katja Luck: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  2. Dae-Kyum Kim: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  3. Luke Lambourne: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  4. Kerstin Spirohn: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  5. Bridget E Begg: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  6. Wenting Bian: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  7. Ruth Brignall: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  8. Tiziana Cafarelli: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  9. Francisco J Campos-Laborie: Cancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain.
  10. Benoit Charloteaux: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  11. Dongsic Choi: The Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada.
  12. Atina G Coté: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  13. Meaghan Daley: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  14. Steven Deimling: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
  15. Alice Desbuleux: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  16. Amélie Dricot: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  17. Marinella Gebbia: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  18. Madeleine F Hardy: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  19. Nishka Kishore: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  20. Jennifer J Knapp: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  21. István A Kovács: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  22. Irma Lemmens: Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium.
  23. Miles W Mee: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
  24. Joseph C Mellor: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  25. Carl Pollis: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  26. Carles Pons: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
  27. Aaron D Richardson: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  28. Sadie Schlabach: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  29. Bridget Teeking: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  30. Anupama Yadav: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  31. Mariana Babor: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  32. Dawit Balcha: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  33. Omer Basha: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
  34. Christian Bowman-Colin: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  35. Suet-Feung Chin: Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK. ORCID
  36. Soon Gang Choi: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  37. Claudia Colabella: Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy. ORCID
  38. Georges Coppin: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  39. Cassandra D'Amata: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
  40. David De Ridder: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  41. Steffi De Rouck: Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium.
  42. Miquel Duran-Frigola: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
  43. Hanane Ennajdaoui: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  44. Florian Goebels: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
  45. Liana Goehring: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  46. Anjali Gopal: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  47. Ghazal Haddad: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  48. Elodie Hatchi: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  49. Mohamed Helmy: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. ORCID
  50. Yves Jacob: Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS), Paris, France. ORCID
  51. Yoseph Kassa: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  52. Serena Landini: Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  53. Roujia Li: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  54. Natascha van Lieshout: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  55. Andrew MacWilliams: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  56. Dylan Markey: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  57. Joseph N Paulson: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  58. Sudharshan Rangarajan: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  59. John Rasla: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  60. Ashyad Rayhan: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  61. Thomas Rolland: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  62. Adriana San-Miguel: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  63. Yun Shen: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  64. Dayag Sheykhkarimli: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  65. Gloria M Sheynkman: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  66. Eyal Simonovsky: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
  67. Murat Taşan: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  68. Alexander Tejeda: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  69. Vincent Tropepe: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
  70. Jean-Claude Twizere: Molecular Biology of Diseases, Groupe Interdisciplinaire de Génomique Appliquée (GIGA) and Laboratory of Viral Interactomes, University of Liège, Liège, Belgium. ORCID
  71. Yang Wang: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  72. Robert J Weatheritt: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
  73. Jochen Weile: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  74. Yu Xia: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  75. Xinping Yang: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  76. Esti Yeger-Lotem: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. ORCID
  77. Quan Zhong: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  78. Patrick Aloy: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
  79. Gary D Bader: The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. ORCID
  80. Javier De Las Rivas: Cancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), Salamanca, Spain. ORCID
  81. Suzanne Gaudet: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
  82. Tong Hao: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. ORCID
  83. Janusz Rak: The Research Institute of the McGill University Health Centre (RI-MUHC), Montreal, Quebec, Canada. ORCID
  84. Jan Tavernier: Center for Medical Biotechnology, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium.
  85. David E Hill: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. david_hill@dfci.harvard.edu. ORCID
  86. Marc Vidal: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. marc_vidal@dfci.harvard.edu.
  87. Frederick P Roth: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. fritz.roth@utoronto.ca. ORCID
  88. Michael A Calderwood: Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA. michael_calderwood@dfci.harvard.edu. ORCID
PMID: 32296183 DOI: 10.1038/s41586-020-2188-x

Abstract

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships. 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, transcriptome and proteome 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.

References

  1. Vidal, M., Cusick, M. E. & Barabási, A.-L. Interactome networks and human disease. Cell 144, 986–998 (2011). [PMID: 21414488]
  2. Rolland, T. et al. A proteome-scale map of the human interactome network. Cell 159, 1212–1226 (2014). [PMID: 25416956]
  3. 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). [PMID: 25428349]
  4. Melé, M. et al. The human transcriptome across tissues and individuals. Science 348, 660–665 (2015). [PMID: 25954002]
  5. Thul, P. J. et al. A subcellular map of the human proteome. Science 356, eaal3321 (2017). [PMID: 28495876]
  6. Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016). [PMID: 5018207]
  7. The FANTOM Consortium and the RIKEN PMI and CLST (DGT). A promoter-level mammalian expression atlas. Nature 507, 462–470 (2014).
  8. Regev, A. et al. The human cell atlas. eLife 6, e27041 (2017). [PMID: 29206104]
  9. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001). [PMID: 11237011]
  10. Venter, J. C. et al. The sequence of the human genome. Science 291, 1304–1351 (2001). [PMID: 11181995]
  11. Wan, C. et al. Panorama of ancient metazoan macromolecular complexes. Nature 525, 339–344 (2015). [PMID: 26344197]
  12. Hein, M. Y. et al. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 163, 712–723 (2015). [PMID: 26496610]
  13. Huttlin, E. L. et al. Architecture of the human interactome defines protein communities and disease networks. Nature 545, 505–509 (2017). [PMID: 28514442]
  14. Rual, J.-F. et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173–1178 (2005). [PMID: 16189514]
  15. Braun, P. et al. An experimentally derived confidence score for binary protein-protein interactions. Nat. Methods 6, 91–97 (2009). [PMID: 19060903]
  16. Venkatesan, K. et al. An empirical framework for binary interactome mapping. Nat. Methods 6, 83–90 (2009). [PMID: 19060904]
  17. Chen, Y.-C., Rajagopala, S. V., Stellberger, T. & Uetz, P. Exhaustive benchmarking of the yeast two-hybrid system. Nat. Methods 7, 667–668 (2010). [PMID: 20805792]
  18. Choi, S. G. et al. Maximizing binary interactome mapping with a minimal number of assays. Nat. Commun. 10, 3907 (2019). [PMID: 31467278]
  19. Eyckerman, S. et al. Design and application of a cytokine-receptor-based interaction trap. Nat. Cell Biol. 3, 1114–1119 (2001). [PMID: 11781573]
  20. Cassonnet, P. et al. Benchmarking a luciferase complementation assay for detecting protein complexes. Nat. Methods 8, 990–992 (2011). [PMID: 22127214]
  21. Mosca, R., Céol, A. & Aloy, P. Interactome3D: adding structural details to protein networks. Nat. Methods 10, 47–53 (2013). [PMID: 23399932]
  22. 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). [PMID: 25038412]
  23. 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). [PMID: 21176124]
  24. 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). [PMID: 1310259]
  25. Willy, P. J. et al. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 9, 1033–1045 (1995). [PMID: 7744246]
  26. Kovács, I. A. et al. Network-based prediction of protein interactions. Nat. Commun. 10, 1240 (2019). [PMID: 30886144]
  27. Baryshnikova, A. Systematic functional annotation and visualization of biological networks. Cell Syst. 2, 412–421 (2016). [PMID: 27237738]
  28. 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). [PMID: 27974209]
  29. 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). [PMID: 24262037]
  30. 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). [PMID: 22991235]
  31. Jeong, H., Mason, S. P., Barabási, A.-L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001). [PMID: 11333967]
  32. 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). [PMID: 22761559]
  33. Pan, J. et al. Interrogation of mammalian protein complex structure, function, and membership using genome-scale fitness screens. Cell Syst. 6, 555–568 (2018). [PMID: 29778836]
  34. Yu, H. et al. High-quality binary protein interaction map of the yeast interactome network. Science 322, 104–110 (2008). [PMID: 18719252]
  35. Kim, D. K. et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics 31, 933–939 (2015). [PMID: 25388151]
  36. Hessvik, N. P. & Llorente, A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci. 75, 193–208 (2018). [PMID: 28733901]
  37. Imjeti, N. S. et al. Syntenin mediates SRC function in exosomal cell-to-cell communication. Proc. Natl Acad. Sci. USA 114, 12495–12500 (2017). [PMID: 29109268]
  38. Calderone, A., Castagnoli, L. & Cesareni, G. mentha: a resource for browsing integrated protein-interaction networks. Nat. Methods 10, 690–691 (2013). [PMID: 23900247]
  39. Kiran, M. & Nagarajaram, H. A. Global versus local hubs in human protein-protein interaction network. J. Proteome Res. 12, 5436–5446 (2013). [PMID: 24050456]
  40. 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). [PMID: 26897376]
  41. Paulson, J. N. et al. Tissue-aware RNA-Seq processing and normalization for heterogeneous and sparse data. BMC Bioinformatics 18, 437 (2017). [PMID: 28974199]
  42. Bossi, A. & Lehner, B. Tissue specificity and the human protein interaction network. Mol. Syst. Biol. 5, 260 (2009). [PMID: 19357639]
  43. 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). [PMID: 24921629]
  44. Sahni, N. et al. Widespread macromolecular interaction perturbations in human genetic disorders. Cell 161, 647–660 (2015). [PMID: 25910212]
  45. 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). [PMID: 22508754]
  46. Landrum, M. J. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46 (D1), D1062–D1067 (2018). [PMID: 29165669]
  47. Bhatnagar, S. et al. TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein. Nature 516, 116–120 (2014). [PMID: 25470042]
  48. 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). [PMID: 25801283]
  49. Novarino, G. et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343, 506–511 (2014). [PMID: 24482476]
  50. Yang, X. et al. Widespread expansion of protein interaction capabilities by alternative splicing. Cell 164, 805–817 (2016). [PMID: 26871637]

Grants

  1. U01 HG007690/NHGRI NIH HHS
  2. P50 HG004233/NHGRI NIH HHS
  3. R01 GM109199/NIGMS NIH HHS
  4. U41 HG001715/NHGRI NIH HHS
  5. U01 HL098166/NHLBI NIH HHS
  6. T32 CA009361/NCI NIH HHS

MeSH Term

Extracellular Space
Humans
Organ Specificity
Protein Interaction Mapping
Proteome

Chemicals

Proteome
Journal Article

Links to CNCB-NGDC Resources

Database Commons: DBC008294 (HuRI)
Article has an altmetric score of 432

Word Cloud

Created with Highcharts 10.0.0interactionscellularHuRIinteractomehumanreferencegenomefunctionnetworksmapbinaryproteinapproximatelyprotein-proteintissue-specificGlobalinsightsorganizationrequirecomprehensiveunderstandingmediategenotype-phenotyperelationshipspresent'all-by-all''HuRI'53000fourtimesmanyhigh-qualitycuratedsmall-scalestudiesintegrationtranscriptomeproteomedataenablesstudiedwithinphysiologicalpathologicalcontextsdemonstrateutilityidentifyingspecificsubcellularrolesInferredrevealgeneralprinciplesformationcontext-specificfunctionselucidatepotentialmolecularmechanismsmightunderliephenotypesMendeliandiseasessystematicproteome-widelinksgenomicvariationphenotypicoutcomes

Similar Articles

Cited By (539)