Protein identification by spectral networks analysis

peer-reviewed · Proceedings of the National Academy of Sciences · 2007

peer-reviewed · Proceedings of the National Academy of Sciences · 2007. Nuno Bandeira et al. Advances in tandem mass spectrometry (MS/MS) steadily increase the rate of generation of MS/MS spectra. As a…
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) 160
Venue 2-year citedness 8.56

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.

Authors

  1. Nuno Bandeira · University of California San Diego, University of California System
  2. Dekel Tsur · University of California San Diego
  3. Ari Frank · Affectivon, Inc., Max Planck Institute of Molecular Cell Biology and Genetics, University of California San Diego
  4. Pavel A. Pevzner · Max Planck Institute of Molecular Cell Biology and Genetics, Saint Petersburg Academic University, St Petersburg University, St. Petersburg State University, University of California San Diego, University of Southern California

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.

Cites (12)

Cited by (21)

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