Multi-spectra peptide sequencing and its applications to multistage mass spectrometry.
Despite a recent surge of interest in database-independent peptide identifications, accurate de novo peptide sequencing remains an elusive goal. While the recently introduced spectral network approach resulted in accurate peptide sequencing in low-complexity samples, its success depends on the chance of presence of spectra from overlapping peptides. On the other hand, while multistage mass spectrometry (collecting multiple MS 3 spectra from each MS 2 spectrum) can be applied to all spectra in a complex sample, there are currently no software tools for de novo peptide sequencing by multistage mass spectrometry. We describe a rigorous probabilistic framework for analyzing spectra of overlapping peptides and show how to apply it for multistage mass spectrometry. Our software results in both accurate de novo peptide sequencing from multistage mass spectra (despite the inferior quality of MS 3 spectra) and improved interpretation of spectral networks. We further study the problem of de novo peptide sequencing with accurate parent mass (but inaccurate fragment masses), the protocol that may soon become the dominant mode of spectral acquisition. Most existing peptide sequencing algorithms (based on the spectrum graph approach) do not track the accurate parent mass and are thus not equipped for solving this problem. We describe a de novo peptide sequencing algorithm aimed at this experimental protocol and show that it improves the sequencing accuracy on both tandem and multistage mass spectrometry.
Bandeira
Nuno
N
Department of Computer Science and Engineering, University of California, San Diego, USA. bandeira@ucsd.edu
Olsen
Jesper V
JV
Mann
Jesper V
JV
Mann
Matthias
M
Pevzner
Pavel A
PA
D019295:Computational Biology; D005656:Fungal Proteins / Q000032:analysis*; D010455:Peptides / Q000032:analysis*; D020539:Sequence Analysis, Protein / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015003:Yeasts / Q000737:chemistry*
D005656:Fungal Proteins; D010455:Peptides
Mol Syst Biol. 2007;3:102
17437027
Mol Cell Proteomics. 2008 Jan;7(1):71-87
17872894
Anal Chem. 2005 Feb 15;77(4):964-73
15858974
Anal Chem. 1998 Dec 15;70(24):5162-5
9868913
Mol Cell Proteomics. 2007 Jun;6(6):973-86
17317661
Nat Biotechnol. 2005 Dec;23(12):1562-7
16311586
J Comput Biol. 1999 Fall-Winter;6(3-4):327-42
10582570
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6140-5
17404225
Drug Discov Today. 2006 Jul;11(13-14):655-60
16793535
Anal Biochem. 2006 May 1;352(1):77-86
16545334
Genome Res. 2007 Sep;17(9):1362-77
17690205
Anal Chem. 2004 Dec 15;76(24):7221-33
15595863
J Pept Sci. 2005 Nov;11(11):670-6
16103988
Mol Cell Proteomics. 2007 Jul;6(7):1123-34
17446555
Anal Chem. 2007 Jul 1;79(13):4870-8
17550227
J Comput Biol. 2001;8(3):325-37
11535179
Rapid Commun Mass Spectrom. 1997;11(9):1015-24
9204576
J Proteome Res. 2006 Nov;5(11):3018-28
17081053
Electrophoresis. 1999 Dec;20(18):3551-67
10612281
Nature. 2003 Mar 13;422(6928):198-207
12634793
Bioinformatics. 2005 Oct 1;21(19):3726-32
16105903
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13417-22
15347803
Annu Rev Genet. 2005;39:23-46
16285851
Anal Chem. 2005 Nov 15;77(22):7265-73
16285674
Biomed Environ Mass Spectrom. 1990;19(6):363-8
24730078
Genome Res. 2007 Feb;17(2):231-9
17189379
Anal Chem. 2000 Jun 1;72(11):2337-50
10857603
Rapid Commun Mass Spectrom. 2003;17(20):2337-42
14558135
Comput Appl Biosci. 1995 Aug;11(4):427-34
8521052
Anal Chem. 2005 Jul 15;77(14):4626-39
16013882
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2795-800
12591958
Anal Chem. 1995 Sep 15;67(18):3202-10
8686885