Prediction of novel modifications by unrestrictive search of tandem mass spectra.
Post-translational modifications (PTMs) greatly increase the complexity and diversity of the proteome so that a protein can carry out a wide variety of functions. PTM prediction on proteins is one of the major challenges in proteomics research. Various approaches have been developed for an unrestrictive search of PTMs in proteins using tandem mass spectrometry (MS/MS). However, most tools usually addressed frequent modifications despite the fact that critical biological modifications may be rare. Here, we present MODmap for exploring potentially important rare and unknown modifications from MS/MS spectra. Extended sequence tag-based spectral alignment is proposed. It is highly sensitive to modified regions in an MS/MS spectrum and is tolerant of multiple modifications per peptide. We have developed an unrestrictive algorithm (MOD(i)), which rapidly searches for all known types of PTMs at once, without limiting a multitude of modified sites in a peptide. After MOD(i) produces spectral alignment results using all known types of PTMs, high-quality spectral alignments are subject to MODmap and are re-estimated. New mass offsets are reported via local alignment and MODmap determines novel modification candidates. In analyses of PTM-rich lens proteins, our methodology was demonstrated to be sensitive to rare modifications and suggested several confident novel modification candidates.
Na
Seungjin
S
Department of Mechanical and Information Engineering, University of Seoul, Seoul, Korea.
Paek
Eunok
E
D000369:Aged, 80 and over; D000465:Algorithms; D003198:Computer Simulation; D030562:Databases, Protein; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry; D008297:Male; D010446:Peptide Fragments / Q000032:analysis*; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D010446:Peptide Fragments