Adaptive discriminant function analysis and reranking of MS/MS database search results for improved peptide identification in shotgun proteomics.
Robust statistical validation of peptide identifications obtained by tandem mass spectrometry and sequence database searching is an important task in shotgun proteomics. PeptideProphet is a commonly used computational tool that computes confidence measures for peptide identifications. In this paper, we investigate several limitations of the PeptideProphet modeling approach, including the use of fixed coefficients in computing the discriminant search score and selection of the top scoring peptide assignment per spectrum only. To address these limitations, we describe an adaptive method in which a new discriminant function is learned from the data in an iterative fashion. We extend the modeling framework to go beyond the top scoring peptide assignment per spectrum. We also investigate the effect of clustering the spectra according to their spectrum quality score followed by cluster-specific mixture modeling. The analysis is carried out using data acquired from a mixture of purified proteins on four different types of mass spectrometers, as well as using a complex human serum data set. A special emphasis is placed on the analysis of data generated on high mass accuracy instruments.
Ding
Ying
Y
Department of Pathology, Department of Biostatistics, and Center for Computational Biology and Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Choi
Hyungwon
H
Nesvizhskii
Alexey I
AI
D000465:Algorithms; D001798:Blood Proteins / Q000032:analysis; D030562:Databases, Protein; D016002:Discriminant Analysis; D006801:Humans; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
D001798:Blood Proteins; D010455:Peptides
Nat Methods. 2004 Dec;1(3):195-202
15789030
Nat Methods. 2007 Oct;4(10):787-97
17901868
Mol Cell Proteomics. 2005 Dec;4(12):2010-21
16249172
J Proteome Res. 2008 Jan;7(1):35-9
18067248
Proteomics. 2004 Apr;4(4):961-9
15048978
J Proteome Res. 2008 Jan;7(1):96-103
17711323
Anal Chem. 2004 Dec 1;76(23):6853-60
15571333
Mol Cell Proteomics. 2008 Jun;7(6):1135-45
18303013
J Proteome Res. 2003 Mar-Apr;2(2):137-46
12716127
Mol Cell Proteomics. 2006 Mar;5(3):497-509
16321970
J Proteome Res. 2008 Jan;7(1):286-92
18078310
Mol Cell Proteomics. 2007 Mar;6(3):527-36
17164401
Nat Methods. 2007 Mar;4(3):207-14
17327847
Anal Chem. 2003 Feb 15;75(4):768-74
12622365
Mol Cell Proteomics. 2004 Jun;3(6):531-3
15075378
J Proteome Res. 2008 Jun;7(6):2195-203
18422353
Nat Rev Mol Cell Biol. 2004 Sep;5(9):699-711
15340378
J Proteome Res. 2008 Jan;7(1):47-50
18067251
Methods Enzymol. 2005;402:289-312
16401513
Mol Cell Proteomics. 2006 Jul;5(7):1326-37
16635985
J Proteome Res. 2008 Jan;7(1):245-53
18173222
Mol Cell Proteomics. 2004 Jun;3(6):608-14
15034119
Anal Chem. 2002 Oct 15;74(20):5383-92
12403597
J Proteome Res. 2004 Jul-Aug;3(4):760-9
15359729
Anal Bioanal Chem. 2007 Nov;389(5):1409-19
17874083
Electrophoresis. 1999 Dec;20(18):3551-67
10612281
J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89
24226387
Nature. 2003 Mar 13;422(6928):198-207
12634793
Anal Chem. 2007 Aug 1;79(15):5620-32
17580982
Mol Cell Proteomics. 2008 Jun;7(6):1124-34
18303012
Nat Methods. 2007 Nov;4(11):923-5
17952086
Bioinformatics. 2008 Apr 1;24(7):1021-3
18304935
J Proteome Res. 2007 Feb;6(2):828-36
17269739
Mol Cell Proteomics. 2005 Aug;4(8):1194-204
15937296
J Proteome Res. 2008 Jan;7(1):40-4
18052118
Mol Cell Proteomics. 2008 May;7(5):962-70
18216375
J Proteome Res. 2006 Apr;5(4):1003-9
16602709
Mol Cell Proteomics. 2007 Sep;6(9):1589-98
17533221
Mol Cell Proteomics. 2005 Oct;4(10):1419-40
16009968
J Proteome Res. 2005 Jul-Aug;4(4):1353-60
16083287
Mol Cell Proteomics. 2007 Mar;6(3):377-81
17164402
Bioinformatics. 2004 Jun 12;20(9):1466-7
14976030
Anal Chem. 2003 Sep 1;75(17):4646-58
14632076
J Proteome Res. 2008 Jan;7(1):254-65
18159924
Anal Chem. 2004 Jul 1;76(13):3556-68
15228325
Anal Chem. 2005 Jul 15;77(14):4626-39
16013882
Mol Cell Proteomics. 2006 Apr;5(4):652-70
16352522