title: Identification of additional proteins in differential proteomics using protein interaction networks.
abstract: In this study, we developed a novel computational approach based on protein-protein interaction networks to identify a list of proteins that might have remained undetected in differential proteomic profiling experiments. We tested our computational approach on two sets of human smooth muscle cell protein extracts that were affected differently by DNase I treatment. Differential proteomic analysis by saturation DIGE resulted in the identification of 41 human proteins. The application of our approach to these 41 input proteins consisted of four steps: (i) Compilation of a human protein-protein interaction network from public databases; (ii) calculation of interaction scores based on functional similarity; (iii) determination of a set of candidate proteins that are needed to efficiently and confidently connect the 41 input proteins; and (iv) ranking of the resulting 25 candidate proteins. Two of the three highest-ranked proteins, beta-arrestin 1, and beta-arrestin 2, were experimentally tested, revealing that their abundance levels in human smooth muscle cell samples were indeed affected by DNase I treatment. These proteins had not been detected during the experimental proteomic analysis. Our study suggests that our computational approach may represent a simple, universal, and cost-effective means to identify additional proteins that remain elusive for current 2D gel-based proteomic profiling techniques.
authors: Department of Genomes and Genetics, Systems Biology Laboratory, Institut Pasteur, Paris, France.
authors: Frederik
authors: F
authors: Gwinner
authors: Adelina E
authors: AE
authors: Acosta-Martin
authors: Ludovic
authors: L
authors: Boytard
authors: Maggy
authors: M
authors: Chwastyniak
authors: Olivia
authors: O
authors: Beseme
authors: Hervé
authors: H
authors: Drobecq
authors: Sophie
authors: S
authors: Duban-Deweer
authors: Francis
authors: F
authors: Juthier
authors: Brigitte
authors: B
authors: Jude
authors: Philippe
authors: P
authors: Amouyel
authors: Florence
authors: F
authors: Pinet
authors: Benno
authors: B
authors: Schwikowski
mesh_terms: D002457:Cell Extracts; D002478:Cells, Cultured; D030562:Databases, Protein; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012984:Software
chemical_list: D002457:Cell Extracts; D009124:Muscle Proteins
references: Mol Syst Biol. 2009;5:303
references: 19690572
references: Nature. 2011 Feb 10;470(7333):163-5
references: 21307913
references: J Biol Chem. 1975 May 25;250(10):4007-21
references: 236308
references: Nat Protoc. 2007;2(10):2366-82
references: 17947979
references: Nucleic Acids Res. 2012 Jul;40(Web Server issue):W505-9
references: 22638579
references: Proteomics. 2007 Aug;7(15):2541-52
references: 17647236
references: Proteomics. 2003 Jul;3(7):1181-95
references: 12872219
references: PLoS One. 2009 Jun 05;4(6):e5815
references: 19503833
references: Mol Cell Proteomics. 2005 May;4(5):683-92
references: 15722371
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D396-403
references: 18957448
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D525-31
references: 19850723
references: J Proteomics. 2010 Oct 10;73(11):2277-89
references: 20637909
references: Methods Enzymol. 2009;463:515-40
references: 19892190
references: Nat Biotechnol. 2000 Dec;18(12):1257-61
references: 11101803
references: Methods Mol Biol. 2011;696:3-26
references: 21063938
references: Sci Signal. 2009 Jul 28;2(81):ra40
references: 19638617
references: J Proteome Res. 2008 Sep;7(9):4107-18
references: 18698805
references: Nat Methods. 2009 Jun;6(6):423-30
references: 19448641
references: Bioinformatics. 2009 Nov 15;25(22):2955-61
references: 19633097
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D434-9
references: 17932054
references: J Proteome Res. 2008 Aug;7(8):3572-82
references: 18549265
references: Nucleic Acids Res. 2001 Jan 1;29(1):242-5
references: 11125103
references: Brief Bioinform. 2006 Sep;7(3):243-55
references: 16880171
references: Anal Bioanal Chem. 2007 Oct;389(4):1017-31
references: 17668192