Unrestrictive identification of multiple post-translational modifications from tandem mass spectrometry using an error-tolerant algorithm based on an extended sequence tag approach.
Identification of post-translational modifications (PTMs) is important to understanding the biological functions of proteins. MS/MS is a useful tool to identify PTMs. Most existing search tools are restricted to take only a few types of PTMs as input. Here we describe a new algorithm, called MOD(i) (pronounced "mod eye"), that rapidly searches for all known types of PTMs at once without limiting a multitude of modified sites in a peptide. MOD(i) introduces the notion of a tag chain, a combination structure made from multiple sequence tags, that effectively localizes modified regions within a spectrum and overcomes de novo sequencing errors common in tag-based approaches. MOD(i) showed its performance competence by identifying various types of PTMs in analysis of PTM-rich proteins such as glyceraldehyde-3-phosphate dehydrogenase and lens protein. We demonstrated that MOD(i) innovatively manages the computational complexity of identifying multiple PTMs in a peptide, which may exist in a greater variety than usually expected. In addition, it is suggested that MOD(i) has great potential to discover novel modifications.
Na
Seungjin
S
Department of Mechanical and Information Engineering, University of Seoul, Seoul, 130-743, Korea.
Jeong
Jaeho
J
Park
Heejin
H
Lee
Kong-Joo
KJ
Paek
Eunok
E
D000369:Aged, 80 and over; D000465:Algorithms; D000595:Amino Acid Sequence; D002386:Cataract / Q000378:metabolism; D030562:Databases, Protein; D005136:Eye Proteins / Q000032:analysis / Q000737:chemistry; D005189:False Positive Reactions; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000737:chemistry; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D012044:Regression Analysis; D012984:Software; D053719:Tandem Mass Spectrometry / Q000379:methods*
D005136:Eye Proteins; D010455:Peptides; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)