Estimating dispensable content in the human interactome.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 07 2019
19 07 2019
Historique:
received:
03
12
2018
accepted:
21
06
2019
entrez:
21
7
2019
pubmed:
22
7
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Protein-protein interaction (PPI) networks (interactome networks) have successfully advanced our knowledge of molecular function, disease and evolution. While much progress has been made in quantifying errors and biases in experimental PPI datasets, it remains unknown what fraction of the error-free PPIs in the cell are completely dispensable, i.e., effectively neutral upon disruption. Here, we estimate dispensable content in the human interactome by calculating the fractions of PPIs disrupted by neutral and non-neutral mutations. Starting with the human reference interactome determined by experiments, we construct a human structural interactome by building homology-based three-dimensional structural models for PPIs. Next, we map common mutations from healthy individuals as well as Mendelian disease-causing mutations onto the human structural interactome, and perform structure-based calculations of how these mutations perturb the interactome. Using our predicted as well as experimentally-determined interactome perturbation patterns by common and disease mutations, we estimate that <~20% of the human interactome is completely dispensable.
Identifiants
pubmed: 31324802
doi: 10.1038/s41467-019-11180-2
pii: 10.1038/s41467-019-11180-2
pmc: PMC6642175
doi:
Substances chimiques
Carrier Proteins
0
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3205Références
Nucleic Acids Res. 2001 Jan 1;29(1):308-11
pubmed: 11125122
Cell. 2016 Jan 14;164(1-2):310-323
pubmed: 26771498
PLoS Comput Biol. 2017 Aug 28;13(8):e1005717
pubmed: 28846689
Nat Rev Genet. 2017 Sep;18(9):551-562
pubmed: 28607512
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90
pubmed: 17502601
Nucleic Acids Res. 2016 Jan 4;44(D1):D710-6
pubmed: 26687719
Nature. 2014 Mar 27;507(7493):462-70
pubmed: 24670764
Brookhaven Symp Biol. 1972;23:366-70
pubmed: 5065367
Bioinformatics. 2013 Jun 15;29(12):1577-9
pubmed: 23599502
Sci Signal. 2013 May 21;6(276):ra38
pubmed: 23695164
Nat Struct Biol. 2003 Dec;10(12):980
pubmed: 14634627
Nature. 2002 May 23;417(6887):399-403
pubmed: 12000970
Nat Biotechnol. 2012 Jan 15;30(2):159-64
pubmed: 22252508
Curr Opin Struct Biol. 2011 Feb;21(1):50-61
pubmed: 21071205
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Science. 2006 Dec 22;314(5807):1938-41
pubmed: 17185604
Nat Methods. 2013 Jan;10(1):47-53
pubmed: 23399932
Cell. 2014 Nov 20;159(5):1212-1226
pubmed: 25416956
Bioinformatics. 2009 Jun 1;25(11):1422-3
pubmed: 19304878
Bioinformatics. 2019 Feb 1;35(3):462-469
pubmed: 30020414
Mol Syst Biol. 2016 Apr 22;12(4):865
pubmed: 27107014
Nucleic Acids Res. 2014 Jan;42(Database issue):D191-8
pubmed: 24253303
Am J Hum Genet. 2013 Jul 11;93(1):78-89
pubmed: 23791107
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W382-8
pubmed: 15980494
Nucleic Acids Res. 2014 Jan;42(Database issue):D358-63
pubmed: 24234451
Biol Open. 2018 Jul 23;7(7):
pubmed: 30037883
Genome Biol Evol. 2017 Jul 1;9(7):1880-1885
pubmed: 28854598
Nucleic Acids Res. 2016 Jan 4;44(D1):D862-8
pubmed: 26582918
Nature. 2006 Nov 16;444(7117):279-80
pubmed: 17051147
Elife. 2016 Apr 25;5:
pubmed: 27111525
PLoS Genet. 2012;8(12):e1003161
pubmed: 23300466
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Cell Rep. 2015 Feb 24;10(7):1202-14
pubmed: 25704821
Cell. 2018 Sep 20;175(1):40-42
pubmed: 30241614
Curr Opin Struct Biol. 2017 Jun;44:201-210
pubmed: 28575754
Mol Syst Biol. 2007;3:88
pubmed: 17353930
Nucleic Acids Res. 2013 Jan;41(Database issue):D377-86
pubmed: 23193289
Nat Genet. 2014 Jun;46(6):583-7
pubmed: 24816255
Science. 2016 Oct 14;354(6309):229-232
pubmed: 27738172
Cell. 2015 Apr 23;161(3):647-660
pubmed: 25910212
Nat Rev Genet. 2007 Oct;8(10):803-13
pubmed: 17878896
Cell. 2011 Mar 18;144(6):986-98
pubmed: 21414488
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Trends Genet. 2009 May;25(5):193-7
pubmed: 19349092
J Mol Biol. 2013 Apr 26;425(8):1363-77
pubmed: 23376099
J Mol Biol. 2013 Nov 1;425(21):3949-63
pubmed: 23867278
Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10965-10970
pubmed: 30301792
Nat Methods. 2015 Mar;12(3):167-8
pubmed: 25719824
Cell. 2018 Sep 20;175(1):239-253.e17
pubmed: 30197081
Am J Hum Genet. 2007 Apr;80(4):727-39
pubmed: 17357078
PLoS Pathog. 2013;9(12):e1003778
pubmed: 24339775
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8725-30
pubmed: 21555556
Nature. 2006 Nov 16;444(7117):383-6
pubmed: 17051159
Science. 2015 Feb 20;347(6224):1257601
pubmed: 25700523
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10538-43
pubmed: 21680884
Philos Trans R Soc Lond B Biol Sci. 2012 Sep 19;367(1602):2594-606
pubmed: 22889910
Curr Opin Genet Dev. 2013 Dec;23(6):649-57
pubmed: 24287335
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Cell. 2013 Nov 21;155(5):983-9
pubmed: 24267884
Cell. 2016 Feb 11;164(4):805-17
pubmed: 26871637
BMC Bioinformatics. 2008 Apr 29;9 Suppl 5:S4
pubmed: 18460186
Sci Signal. 2009 Mar 03;2(60):pe11
pubmed: 19261595
J Mol Biol. 2017 Feb 3;429(3):426-434
pubmed: 27899282
Curr Opin Struct Biol. 2013 Dec;23(6):941-53
pubmed: 24007795
J Mol Biol. 1990 Oct 5;215(3):403-10
pubmed: 2231712
Prog Biophys Mol Biol. 2017 Sep;128:3-13
pubmed: 27913149
Curr Opin Struct Biol. 2018 Jun;50:42-48
pubmed: 29112911
Nat Commun. 2014 Jun 26;5:4212
pubmed: 24967666
Biochemistry. 1999 Oct 12;38(41):13560-73
pubmed: 10521263
Clin Cancer Res. 2000 Jun;6(6):2138-45
pubmed: 10873062