Identification of post-translational modifications by blind search of mass spectra.
Most tandem mass spectrometry (MS/MS) database search algorithms perform a restrictive search that takes into account only a few types of post-translational modifications (PTMs) and ignores all others. We describe an unrestrictive PTM search algorithm, MS-Alignment, that searches for all types of PTMs at once in a blind mode, that is, without knowing which PTMs exist in nature. Blind PTM identification makes it possible to study the extent and frequency of different types of PTMs, still an open problem in proteomics. Application of this approach to lens proteins resulted in the largest set of PTMs reported in human crystallins so far. Our analysis of various MS/MS data sets implies that the biological phenomenon of modification is much more widespread than previously thought. We also argue that MS-Alignment reveals some uncharacterized modifications that warrant further experimental validation.
Tsur
Dekel
D
Department of Computer Science and Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0404, USA.
Tanner
Stephen
S
Zandi
Ebrahim
E
Bafna
Vineet
V
Pevzner
Pavel A
PA
D000465:Algorithms; D000595:Amino Acid Sequence; D001185:Artificial Intelligence; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism*; D007908:Lens, Crystalline / Q000737:chemistry* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated / Q000379:methods; D010449:Peptide Mapping / Q000379:methods; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid
D003459:Crystallins; D020543:Proteome