title: Reconstituting protein interaction networks using parameter-dependent domain-domain interactions.
abstract: BACKGROUND
  We can describe protein-protein interactions (PPIs) as sets of distinct domain-domain interactions (DDIs) that mediate the physical interactions between proteins. Experimental data confirm that DDIs are more consistent than their corresponding PPIs, lending support to the notion that analyses of DDIs may improve our understanding of PPIs and lead to further insights into cellular function, disease, and evolution. However, currently available experimental DDI data cover only a small fraction of all existing PPIs and, in the absence of structural data, determining which particular DDI mediates any given PPI is a challenge.
  
  
  RESULTS
  We present two contributions to the field of domain interaction analysis. First, we introduce a novel computational strategy to merge domain annotation data from multiple databases. We show that when we merged yeast domain annotations from six annotation databases we increased the average number of domains per protein from 1.05 to 2.44, bringing it closer to the estimated average value of 3. Second, we introduce a novel computational method, parameter-dependent DDI selection (PADDS), which, given a set of PPIs, extracts a small set of domain pairs that can reconstruct the original set of protein interactions, while attempting to minimize false positives. Based on a set of PPIs from multiple organisms, our method extracted 27% more experimentally detected DDIs than existing computational approaches.
  
  
  CONCLUSIONS
  We have provided a method to merge domain annotation data from multiple sources, ensuring large and consistent domain annotation for any given organism. Moreover, we provided a method to extract a small set of DDIs from the underlying set of PPIs and we showed that, in contrast to existing approaches, our method was not biased towards DDIs with low or high occurrence counts. Finally, we used these two methods to highlight the influence of the underlying annotation density on the characteristics of extracted DDIs. Although increased annotations greatly expanded the possible DDIs, the lack of knowledge of the true biological false positive interactions still prevents an unambiguous assignment of domain interactions responsible for all protein network interactions.Executable files and examples are given at: http://www.bhsai.org/downloads/padds/
authors: Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702, USA.
authors: Vesna
authors: V
authors: Memišević
authors: Anders
authors: A
authors: Wallqvist
authors: Jaques
authors: J
authors: Reifman
mesh_terms: D030562:Databases, Protein; D058977:Molecular Sequence Annotation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins
references: Nature. 1999 Nov 4;402(6757):86-90
references: 10573422
references: Science. 1999 Jul 30;285(5428):751-3
references: 10427000
references: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D413-7
references: 15608228
references: Nat Methods. 2009 Jan;6(1):83-90
references: 19060904
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D300-4
references: 18953040
references: BMC Bioinformatics. 2009 Aug 05;10:241
references: 19656385
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D656-61
references: 17913741
references: Proc Natl Acad Sci U S A. 2008 May 13;105(19):6959-64
references: 18474861
references: Proc Natl Acad Sci U S A. 1998 May 26;95(11):5857-64
references: 9600884
references: BMC Bioinformatics. 2006 May 25;7:269
references: 16725050
references: Bioinformatics. 2005 Apr 1;21(7):993-1001
references: 15509600
references: Nature. 2002 May 23;417(6887):399-403
references: 12000970
references: PLoS One. 2009 Dec 21;4(12):e8378
references: 20041107
references: J Mol Biol. 2001 Jul 6;310(2):311-25
references: 11428892
references: Genome Biol. 2006;7(12):R125
references: 17184549
references: IEEE/ACM Trans Comput Biol Bioinform. 2007 Jan-Mar;4(1):78-87
references: 17277415
references: Genome Inform. 2004;15(1):56-68
references: 15712110
references: Bioinformatics. 2005 Feb 1;21(3):410-2
references: 15353450
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22
references: 19920124
references: Genome Res. 2002 Oct;12(10):1540-8
references: 12368246
references: Nucleic Acids Res. 2001 Jan 1;29(1):41-3
references: 11125044
references: PLoS Comput Biol. 2009 Sep;5(9):e1000515
references: 19779545
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D211-5
references: 18940856
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D225-9
references: 21109532
references: Bioinformatics. 2000 Dec;16(12):1145-50
references: 11159333
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D730-5
references: 21113022
references: PLoS Comput Biol. 2006 Aug 25;2(8):e114
references: 16933986
references: Bioinformatics. 2005 Dec 15;21(24):4394-400
references: 16234318
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D229-32
references: 18978020
references: Science. 2008 Oct 3;322(5898):104-10
references: 18719252
references: Proteins. 2010 Apr;78(5):1243-53
references: 20027642
references: Nature. 2003 Dec 18;426(6968):884-90
references: 14685248
references: Genome Biol. 2005;6(10):R89
references: 16207360
references: Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:783-6
references: 21096109
references: BMC Bioinformatics. 2012 May 04;13:79
references: 22558947
references: J Mol Biol. 2001 Nov 2;313(4):903-19
references: 11697912
references: Genome Biol. 2006;7(11):R104
references: 17094802
references: Bioinformatics. 2009 Oct 1;25(19):2492-9
references: 19667081
references: Mol Cell Proteomics. 2011 Dec;10(12):M111.012500
references: 21876202
references: Genome Biol. 2006;7(11):120
references: 17147767
references: J Mol Biol. 2005 Apr 22;348(1):231-43
references: 15808866
references: BMC Bioinformatics. 2008 Mar 26;9:171
references: 18366803
references: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D212-5
references: 15608179
references: BMC Bioinformatics. 2010 Dec 21;11:605
references: 21176124
references: Nat Methods. 2009 Jan;6(1):39-46
references: 19116613
references: J Mol Biol. 2001 Aug 24;311(4):681-92
references: 11518523
references: Nature. 1997 May 29;387(6632 Suppl):67-73
references: 9169866