InsPecT: Identification of Posttranslationally Modified Peptides from Tandem Mass Spectra

peer-reviewed · Analytical Chemistry · 2005

peer-reviewed · Analytical Chemistry · 2005. Stephen Tanner et al. Reliable identification of posttranslational modifications is key to understanding various cellular…
Date 2005-07-01
Type peer-reviewed
Venue Analytical Chemistry
Publisher American Chemical Society (ACS)
Contribution adjacent
DOI 10.1021/ac050102d
Citations (OpenAlex) 567
Venue 2-year citedness 7.10

Abstract

Reliable identification of posttranslational modifications is key to understanding various cellular regulatory processes. We describe a tool, InsPecT, to identify posttranslational modifications using tandem mass spectrometry data. InsPecT constructs database filters that proved to be very successful in genomics searches. Given an MS/MS spectrum S and a database D, a database filter selects a small fraction of database D that is guaranteed (with high probability) to contain a peptide that produced S. InsPecT uses peptide sequence tags as efficient filters that reduce the size of the database by a few orders of magnitude while retaining the correct peptide with very high probability. In addition to filtering, InsPecT also uses novel algorithms for scoring and validating in the presence of modifications, without explicit enumeration of all variants. InsPecT identifies modified peptides with better or equivalent accuracy than other database search tools while being 2 orders of magnitude faster than SEQUEST, and substantially faster than X!TANDEM on complex mixtures. The tool was used to identify a number of novel modifications in different data sets, including many phosphopeptides in data provided by Alliance for Cellular Signaling that were missed by other tools.

Authors

  1. Stephen Tanner · University of California San Diego
  2. Hongjun Shu · University of Texas Southwestern Medical Center
  3. Ari Frank · Affectivon, Inc., Max Planck Institute of Molecular Cell Biology and Genetics, University of California San Diego
  4. Ling-Chi Wang · University of Southern California
  5. Ebrahim Zandi · University of Southern California
  6. Marc Mumby · University of Texas Southwestern Medical Center
  7. 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
  8. Vineet Bafna · University of California San Diego

Methods and tools

  • InsPecT: Uses peptide sequence tags derived from the spectrum as a database filter, discarding the vast majority of candidate peptides before scoring, which makes blind searches for post-translational modifications tractable.

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