title: Liquid Chromatography Mass Spectrometry-Based Proteomics: Biological and Technological Aspects.
abstract: Mass spectrometry-based proteomics has become the tool of choice for identifying and quantifying the proteome of an organism. Though recent years have seen a tremendous improvement in instrument performance and the computational tools used, significant challenges remain, and there are many opportunities for statisticians to make important contributions. In the most widely used "bottom-up" approach to proteomics, complex mixtures of proteins are first subjected to enzymatic cleavage, the resulting peptide products are separated based on chemical or physical properties and analyzed using a mass spectrometer. The two fundamental challenges in the analysis of bottom-up MS-based proteomics are: (1) Identifying the proteins that are present in a sample, and (2) Quantifying the abundance levels of the identified proteins. Both of these challenges require knowledge of the biological and technological context that gives rise to observed data, as well as the application of sound statistical principles for estimation and inference. We present an overview of bottom-up proteomics and outline the key statistical issues that arise in protein identification and quantification.
authors: Pacific Northwest National Laboratory, Richland, WA 99352.
authors: Yuliya V
authors: YV
authors: Karpievitch
authors: Ashoka D
authors: AD
authors: Polpitiya
authors: Gordon A
authors: GA
authors: Anderson
authors: Richard D
authors: RD
authors: Smith
authors: Alan R
authors: AR
authors: Dabney
references: J Proteome Res. 2008 Jan;7(1):245-53
references: 18173222
references: Nat Biotechnol. 2001 Mar;19(3):242-7
references: 11231557
references: Methods Mol Biol. 2007;367:261-70
references: 17185781
references: Curr Opin Biotechnol. 2003 Feb;14(1):101-9
references: 12566009
references: J Proteome Res. 2008 Jan;7(1):286-92
references: 18078310
references: Anal Chem. 2003 Mar 15;75(6):1307-15
references: 12659190
references: Nat Methods. 2007 Mar;4(3):207-14
references: 17327847
references: Bioinformatics. 2008 Jan 15;24(2):202-8
references: 18024968
references: Biometrics. 2002 Dec;58(4):701-17
references: 12495124
references: Bioinformatics. 2008 Feb 15;24(4):529-36
references: 18194961
references: Anal Chem. 2009 Aug 1;81(15):6317-26
references: 19586016
references: Anal Chem. 2003 Feb 15;75(4):768-74
references: 12622365
references: Comb Chem High Throughput Screen. 2009 Feb;12(2):137-55
references: 19199883
references: J Proteome Res. 2002 Jul-Aug;1(4):317-23
references: 12645887
references: Anal Chem. 2008 Feb 1;80(3):693-706
references: 18163597
references: J Proteome Res. 2008 Jan;7(1):47-50
references: 18067251
references: Mass Spectrom Rev. 2003 May-Jun;22(3):158-81
references: 12838543
references: Anal Chem. 2002 Oct 15;74(20):5383-92
references: 12403597
references: Anal Chem. 2006 Jul 15;78(14):5026-39
references: 16841926
references: J Biol Chem. 1975 May 25;250(10):4007-21
references: 236308
references: Electrophoresis. 1999 Dec;20(18):3551-67
references: 10612281
references: J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89
references: 24226387
references: Science. 2005 Jun 24;308(5730):1915-20
references: 15879173
references: Electrophoresis. 1998 May;19(6):893-900
references: 9638935
references: J Am Soc Mass Spectrom. 2009 Sep;20(9):1652-9
references: 19523847
references: Methods Enzymol. 2005;402:148-85
references: 16401509
references: Anal Chem. 2001 Dec 1;73(23):5683-90
references: 11774908
references: Mol Cell Proteomics. 2005 Feb;4(2):144-55
references: 15608340
references: Anal Chem. 2005 Feb 15;77(4):964-73
references: 15858974
references: Electrophoresis. 1995 Jun;16(6):1034-59
references: 7498127
references: Anal Chem. 2003 Dec 1;75(23):6415-21
references: 14640709
references: Electrophoresis. 1996 May;17(5):945-53
references: 8783021
references: Bioinformatics. 2009 Oct 1;25(19):2573-80
references: 19602524
references: Nature. 2003 Oct 16;425(6959):737-41
references: 14562106
references: Anal Chem. 2007 Mar 15;79(6):2451-62
references: 17305309
references: J Proteome Res. 2009 May;8(5):2144-56
references: 19222236
references: Brief Funct Genomic Proteomic. 2009 Mar;8(2):136-44
references: 19151093
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Apr 15;866(1-2):48-63
references: 18006394
references: J Proteome Res. 2008 Jan;7(1):29-34
references: 18067246
references: Anal Chem. 2006 Oct 15;78(20):7309-16
references: 17037937
references: Nat Methods. 2004 Dec;1(3):195-202
references: 15789030
references: Anal Chem. 2003 Sep 15;75(18):4818-26
references: 14674459
references: Bioinformatics. 2004 Mar 22;20(5):777-85
references: 14751995
references: Proteomics. 2009 Feb;9(3):499-501
references: 19132688
references: Proteomics. 2007 Feb;7(3):340-50
references: 17177251
references: Biotechnol Genet Eng Rev. 1996;13:19-50
references: 8948108
references: Mass Spectrom Rev. 2004 Jan-Feb;23(1):34-44
references: 14625891
references: Bioinformatics. 2009 Aug 15;25(16):2028-34
references: 19535538
references: Science. 2006 Apr 14;312(5771):212-7
references: 16614208
references: Rapid Commun Mass Spectrom. 2008 Apr;22(7):986-92
references: 18320544
references: J Proteome Res. 2006 Feb;5(2):277-86
references: 16457593
references: Mol Cell Proteomics. 2008 Dec;7(12):2373-85
references: 18644780
references: Nat Methods. 2007 Oct;4(10):787-97
references: 17901868
references: Nat Biotechnol. 2004 Nov;22(11):1459-66
references: 15529173
references: Nat Biotechnol. 2007 Jan;25(1):125-31
references: 17195840
references: Mol Cell Proteomics. 2005 Oct;4(10):1487-502
references: 15979981
references: Appl Microbiol Biotechnol. 2007 Oct;76(6):1223-43
references: 17713763
references: Methods. 2005 Mar;35(3):223-36
references: 15722219
references: Genome Biol. 2006;7(3):401
references: 16563185
references: Humangenetik. 1975;26(3):231-43
references: 1093965
references: Expert Rev Proteomics. 2005 Dec;2(6):839-45
references: 16307524
references: Nat Methods. 2007 Oct;4(10):828-33
references: 17901873
references: Anal Chem. 2008 Nov 15;80(22):8514-25
references: 18855412
references: Curr Genomics. 2009 Apr;10(2):102-9
references: 19794882
references: J Proteome Res. 2008 Nov;7(11):4878-89
references: 18788775
references: Curr Opin Chem Biol. 2006 Feb;10(1):42-9
references: 16418010
references: Anal Chem. 1997 Dec 1;69(23):4751-60
references: 9406525
references: BMC Bioinformatics. 2009 Mar 17;10:87
references: 19292916
references: Methods Mol Biol. 2009;564:13-32
references: 19544015
references: Mol Cell Proteomics. 2004 Dec;3(12):1154-69
references: 15385600
references: Anal Chem. 2002 Sep 15;74(18):4741-9
references: 12349978
references: Nat Med. 2001 Apr;7(4):493-6
references: 11283679
references: J Proteome Res. 2008 Jan;7(1):40-4
references: 18052118
references: Nat Biotechnol. 1999 Oct;17(10):994-9
references: 10504701
references: Annu Int Conf IEEE Eng Med Biol Soc. 2008;2008:3775-8
references: 19163533
references: J Comput Biol. 1999 Fall-Winter;6(3-4):327-42
references: 10582570
references: Lancet. 2002 Feb 16;359(9306):572-7
references: 11867112
references: Nat Biotechnol. 1999 Jul;17(7):676-82
references: 10404161
references: Mol Cell Proteomics. 2002 May;1(5):376-86
references: 12118079
references: Proteomics. 2008 Jul;8(14):2776-7
references: 18655045
references: Anal Chem. 2004 Jul 15;76(14):4193-201
references: 15253663
references: Proteomics. 2004 Dec;4(12):3665-85
references: 15543535
references: Bioinformatics. 2004 Jun 12;20(9):1466-7
references: 14976030
references: J Mass Spectrom. 2004 Oct;39(10):1091-112
references: 15481084
references: Anal Chem. 2003 Sep 1;75(17):4646-58
references: 14632076
references: Nat Chem Biol. 2005 Oct;1(5):252-62
references: 16408053
references: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6591-6
references: 10359756
references: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6
references: 11134512
references: J Am Soc Mass Spectrom. 2000 Apr;11(4):320-32
references: 10757168
references: Methods Mol Biol. 2007;367:87-119
references: 17185772
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Apr 15;877(11-12):1019-39
references: 19297255
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references: 12883005
references: Anal Chem. 1994 Dec 15;66(24):4390-9
references: 7847635
references: J Proteome Res. 2008 Jan;7(1):254-65
references: 18159924
references: PLoS Genet. 2007 Sep;3(9):1724-35
references: 17907809
references: Biosci Rep. 2005 Feb-Apr;25(1-2):71-93
references: 16222421
references: J Comput Biol. 2003;10(1):1-12
references: 12676047
references: Anal Chem. 2008 Feb 15;80(4):961-71
references: 18189369
references: Nat Genet. 2002 Dec;32 Suppl:496-501
references: 12454644
references: Biotechniques. 2004 Oct;37(4):621-4, 626-33, 636 passim
references: 15517975
references: Bioinformatics. 2006 Jul 15;22(14):e307-13
references: 16873487
references: Anal Chem. 2003 Apr 15;75(8):1895-904
references: 12713048
references: Drug Discov Today. 2004 Feb 15;9(4):173-81
references: 14960397
references: Anal Chem. 2005 Jul 15;77(14):4626-39
references: 16013882
references: Curr Opin Struct Biol. 2003 Oct;13(5):595-601
references: 14568614
references: Pac Symp Biocomput. 2006;:315-26
references: 17094249
references: Curr Protoc Protein Sci. 2007 Aug;Chapter 25:Unit25.2
references: 18429324
references: J Proteome Res. 2003 Jan-Feb;2(1):43-50
references: 12643542
references: Curr Opin Chem Biol. 2008 Oct;12(5):483-90
references: 18718552
references: Anal Chem. 2006 Nov 1;78(21):7397-409
references: 17073405