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A New Approach to Protein Identification

  • Nuno Bandeira
  • Dekel Tsur
  • Ari Frank
  • Pavel Pevzner
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3909)

Abstract

Advances in tandem mass-spectrometry (MS/MS) steadily increase the rate of generation of MS/MS spectra and make it more computationally challenging to analyze such huge datasets. As a result, the existing approaches that compare spectra against databases are already facing a bottleneck, particularly when interpreting spectra of post-translationally modified peptides. In this paper we introduce a new idea that allows one to perform MS/MS database search ... without ever comparing a spectrum against a database. The idea has two components: experimental and computational. Our experimental idea is counter- intuitive: we propose to intentionally introduce chemical damage to the sample. Although it does not appear to make any sense from the experimental perspective, it creates a large number of “spectral pairs” that, as we show below, open up computational avenues that were never explored before. 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 very 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 new paradigm for identifying post-translational modifications.

Keywords

Tandem Mass Spectrum Noise Peak Chemical Damage Membership Query Spectral Pair 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Nuno Bandeira
    • 1
  • Dekel Tsur
    • 1
  • Ari Frank
    • 1
  • Pavel Pevzner
    • 1
  1. 1.Dept. of Computer Science and EngineeringUniversity of California, San DiegoLa JollaUSA

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