title: Network-assisted protein identification and data interpretation in shotgun proteomics.
abstract: Protein assembly and biological interpretation of the assembled protein lists are critical steps in shotgun proteomics data analysis. Although most biological functions arise from interactions among proteins, current protein assembly pipelines treat proteins as independent entities. Usually, only individual proteins with strong experimental evidence, that is, confident proteins, are reported, whereas many possible proteins of biological interest are eliminated. We have developed a clique-enrichment approach (CEA) to rescue eliminated proteins by incorporating the relationship among proteins as embedded in a protein interaction network. In several data sets tested, CEA increased protein identification by 8-23% with an estimated accuracy of 85%. Rescued proteins were supported by existing literature or transcriptome profiling studies at similar levels as confident proteins and at a significantly higher level than abandoned ones. Applying CEA on a breast cancer data set, rescued proteins coded by well-known breast cancer genes. In addition, CEA generated a network view of the proteins and helped show the modular organization of proteins that may underpin the molecular mechanisms of the disease.
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232-8340, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Zimmerman
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Park
authors.forename: David L
authors.initials: DL
authors.lastname: Tabb
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Liebler
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D005656:Fungal Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016681:Genome, Fungal; D006801:Humans; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods*; D012984:Software; D049490:Systems Biology
chemical_list: D005656:Fungal Proteins; D010455:Peptides
references.citation: Nature. 2006 Mar 30;440(7084):637-43
references.pmid: 16554755
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: J Proteome Res. 2004 Sep-Oct;3(5):1002-8
references.pmid: 15473689
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D760-5
references.pmid: 17099226
references.citation: Nature. 2001 May 3;411(6833):41-2
references.pmid: 11333967
references.citation: Nat Med. 2006 Apr;12(4):398-400
references.pmid: 16550189
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12123-8
references.pmid: 14517352
references.citation: Nat Rev Cancer. 2006 Oct;6(10):789-802
references.pmid: 16990856
references.citation: Biochim Biophys Acta. 2005 May 20;1749(1):133-41
references.pmid: 15848144
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5890-5
references.pmid: 11983890
references.citation: Nature. 1998 Jun 4;393(6684):440-2
references.pmid: 9623998
references.citation: Science. 2008 Dec 5;322(5907):1511-6
references.pmid: 19023046
references.citation: BMC Bioinformatics. 2006 Nov 18;7:508
references.pmid: 17112386
references.citation: Nature. 2008 Apr 3;452(7187):650-3
references.pmid: 18385740
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2888-93
references.pmid: 14981259
references.citation: Nature. 2005 Jun 9;435(7043):814-8
references.pmid: 15944704
references.citation: Cell. 2006 Apr 7;125(1):173-86
references.pmid: 16615898
references.citation: J Biol Chem. 2002 Jun 21;277(25):22692-8
references.pmid: 11950845
references.citation: Nat Rev Genet. 2004 Feb;5(2):101-13
references.pmid: 14735121
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D41-4
references.pmid: 14681354
references.citation: Cell Cycle. 2007 Dec 1;6(23):2939-43
references.pmid: 18156804
references.citation: Cell. 2006 Apr 7;125(1):187-99
references.pmid: 16615899
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
references.pmid: 15075390
references.citation: Bioinformatics. 2006 Apr 15;22(8):1021-3
references.pmid: 16473872
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W741-8
references.pmid: 15980575
references.citation: Nucleic Acids Res. 2004 Dec 07;32(21):6414-24
references.pmid: 15585665
references.citation: Bioinformatics. 2008 Apr 1;24(7):979-86
references.pmid: 18304937
references.citation: BMC Bioinformatics. 2002 Nov 01;3:34
references.pmid: 12413400
references.citation: Mol Syst Biol. 2007;3:88
references.pmid: 17353930
references.citation: Nature. 2006 Mar 30;440(7084):631-6
references.pmid: 16429126
references.citation: Breast Cancer Res. 2007;9(5):R63
references.pmid: 17897439
references.citation: Anal Chem. 2002 Jul 1;74(13):3076-83
references.pmid: 12141667
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: J Proteome Res. 2007 Oct;6(10):3962-75
references.pmid: 17711321
references.citation: Cancer Res. 2003 Dec 1;63(23):8203-11
references.pmid: 14678976
references.citation: Bioinformatics. 2007 Feb 1;23(3):277-80
references.pmid: 17121779
references.citation: Mol Syst Biol. 2007;3:140
references.pmid: 17940530
references.citation: J Proteome Res. 2007 Feb;6(2):654-61
references.pmid: 17269722
references.citation: Nature. 1999 Dec 2;402(6761 Suppl):C47-52
references.pmid: 10591225
references.citation: Mol Cell Proteomics. 2005 Oct;4(10):1419-40
references.pmid: 16009968
references.citation: Anal Chem. 2003 Sep 1;75(17):4646-58
references.pmid: 14632076
references.citation: Curr Opin Cell Biol. 2007 Apr;19(2):150-8
references.pmid: 17306971
references.citation: Genome Biol. 2006;7(11):120
references.pmid: 17147767
references.citation: BMC Bioinformatics. 2003 Jan 13;4:2
references.pmid: 12525261
references.citation: J Comput Biol. 2006 Mar;13(2):133-44
references.pmid: 16597231
references.citation: Cancer. 2003 Jul 1;98(1):18-23
references.pmid: 12833450
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Jun;69(6 Pt 2):066133
references.pmid: 15244693
references.citation: J Proteome Res. 2007 Sep;6(9):3549-57
references.pmid: 17676885
references.citation: J Med Genet. 2006 Aug;43(8):691-8
references.pmid: 16611749