Protein identification by spectral networks analysis
peer-reviewed · Proceedings of the National Academy of Sciences · 2007
| Date | 2007-04-10 |
| Type | peer-reviewed |
| Venue | Proceedings of the National Academy of Sciences |
| Publisher | National Academy of Sciences |
| Contribution | algorithm |
| DOI | 10.1073/pnas.0701130104 |
| Citations (OpenAlex) | 164 |
| Venue 2-year citedness | 7.84 |
Abstract
Advances in tandem mass spectrometry (MS/MS) steadily increase the rate of generation of MS/MS spectra. As a result, the existing approaches that compare spectra against databases are already facing a bottleneck, particularly when interpreting spectra of modified peptides. Here we explore a concept that allows one to perform an MS/MS database search without ever comparing a spectrum against a database. We propose to take advantage of spectral pairs, which are pairs of spectra obtained from overlapping (often nontryptic) peptides or from unmodified and modified versions of the same peptide. Having a spectrum of a modified peptide paired with a spectrum of an unmodified peptide allows one to separate the prefix and suffix ladders, to greatly reduce the number of noise peaks, and to generate a small number of peptide reconstructions that are likely to contain the correct one. The MS/MS database search is thus reduced to extremely fast pattern-matching (rather than time-consuming matching of spectra against databases). In addition to speed, our approach provides a unique paradigm for identifying posttranslational modifications by means of spectral networks analysis.
Methods and tools
- Shotgun Protein Sequencing: Assembles overlapping MS/MS spectra of related peptides into contigs before any sequence is called, so a protein is sequenced from the assembly rather than from individual spectra. Tolerates mixtures and unanticipated modifications.