Identification of post-translational modifications via blind search of mass-spectra.
Post-translational modifications (PTMs) are of great biological importance. Most existing approaches perform a restrictive search that can only take into account a few types of PTMs and ignore all others. We describe an unrestrictive PTM search algorithm that searches for all types of PTMs at once in a blind mode, i.e., without knowing which PTMs exist in a sample. The blind PTM identification opens a possibility to study the extent and frequencies of different types of PTMs, still an open problem in proteomics. Using our new algorithm, we were able to construct a two-dimensional PTM frequency matrix that reflects the number of MS/MS spectra in a sample for each putative PTM type and each amino acid. Application of this approach to a large IKKb dataset resulted in the largest set of PTMs reported for a single MS/MS sample so far. We demonstrate an excellent correlation between high values in the PTM frequency matrix and known PTMs thus validating our approach. We further argue that the PTM frequency matrix may reveal some still unknown modifications that warrant further experimental validation.
Tsur
Dekel
D
Computer Science and Engineering, University of California at San Diego, USA. dtsur@cs.ucsd.edu
Tanner
Stephen
S
Zandi
Ebrahim
E
Bafna
Vineet
V
Pevzner
Pavel A
PA
D000465:Algorithms; D000595:Amino Acid Sequence; D003628:Database Management Systems; D030562:Databases, Protein; D016247:Information Storage and Retrieval / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*
D011506:Proteins