A turn-key approach for large-scale identification of complex posttranslational modifications.
The conjugation of complex post-translational modifications (PTMs) such as glycosylation and Small Ubiquitin-like Modification (SUMOylation) to a substrate protein can substantially change the resulting peptide fragmentation pattern compared to its unmodified counterpart, making current database search methods inappropriate for the identification of tandem mass (MS/MS) spectra from such modified peptides. Traditionally it has been difficult to develop new algorithms to identify these atypical peptides because of the lack of a large set of annotated spectra from which to learn the altered fragmentation pattern. Using SUMOylation as an example, we propose a novel approach to generate large MS/MS training data from modified peptides and derive an algorithm that learns properties of PTM-specific fragmentation from such training data. Benchmark tests on data sets of varying complexity show that our method is 80-300% more sensitive than current state-of-the-art approaches. The core concepts of our method are readily applicable to developing algorithms for the identifications of peptides with other complex PTMs.
Bioinformatics Program, ∥Skaggs School of Pharmacy and Pharmaceutical Sciences, ⊥Center for Computational Mass Spectrometry, and ¶Department of Computer Science and Engineering, University of California, San Diego , La Jolla, California 92093, United States.
Jian
J
Wang
Veronica G
VG
Anania
Jeff
J
Knott
John
J
Rush
Jennie R
JR
Lill
Philip E
PE
Bourne
Nuno
N
Bandeira
D000465:Algorithms; D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000737:chemistry / Q000378:metabolism; D019985:Benchmarking; D020650:Combinatorial Chemistry Techniques; D030562:Databases, Protein; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis*; D019151:Peptide Library; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D012984:Software; D058207:Sumoylation; D053719:Tandem Mass Spectrometry
D010446:Peptide Fragments; D019151:Peptide Library; D020543:Proteome