Protein identification by spectral networks analysis

Nuno Bandeira, Dekel Tsur, Ari Frank, Pavel A. Pevzner

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

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.

Original languageEnglish
Pages (from-to)6140-6145
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number15
DOIs
StatePublished - 10 Apr 2007
Externally publishedYes

Keywords

  • Alignment
  • Database searching
  • De novo
  • Posttranslational modifications
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • General

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