De Novo Sequencing of Peptides from Top-Down Tandem Mass Spectra

peer-reviewed · Journal of Proteome Research · 2015

peer-reviewed · Journal of Proteome Research · 2015. Kira Vyatkina et al. De novo sequencing of proteins and peptides is one of the most important problems in mass spectrometry-driven…
Date 2015-11-06
Type peer-reviewed
Venue Journal of Proteome Research
Publisher American Chemical Society (ACS)
Contribution algorithm
DOI 10.1021/pr501244v
Citations (OpenAlex) 43
Venue 2-year citedness 3.83

Abstract

De novo sequencing of proteins and peptides is one of the most important problems in mass spectrometry-driven proteomics. A variety of methods have been developed to accomplish this task from a set of bottom-up tandem (MS/MS) mass spectra. However, a more recently emerged top-down technology, now gaining more and more popularity, opens new perspectives for protein analysis and characterization, implying a need for efficient algorithms to process this kind of MS/MS data. Here, we describe a method that allows for the retrieval, from a set of top-down MS/MS spectra, of long and accurate sequence fragments of the proteins contained in the sample. To this end, we outline a strategy for generating high-quality sequence tags from top-down spectra, and introduce the concept of a T-Bruijn graph by adapting to the case of tags the notion of an A-Bruijn graph widely used in genomics. The output of the proposed approach represents the set of amino acid strings spelled out by optimal paths in the connected components of a T-Bruijn graph. We illustrate its performance on top-down data sets acquired from carbonic anhydrase 2 (CAH2) and the Fab region of alemtuzumab.

Authors

  1. Kira Vyatkina · ITMO University, Saint Petersburg Academic University, Saint Petersburg National Research Academic University of the Russian Academy of Sciences, Saint Petersburg State Electrotechnical University, St Petersburg University, St. Petersburg State University
  2. Si Wu · Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, University of Oklahoma
  3. Lennard J. M. Dekker · Erasmus MC, Erasmus University Rotterdam
  4. Martijn M. VanDuijn · Erasmus MC, Erasmus University Rotterdam
  5. Xiaowen Liu · Indiana University Indianapolis, Indiana University School of Medicine, Indiana University-Purdue University Indianapolis, Tulane University, University of Waterloo
  6. Nikola Tolić · Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory
  7. Mikhail Dvorkin · Saint Petersburg Academic University, Saint Petersburg National Research Academic University of the Russian Academy of Sciences
  8. Sonya Alexandrova · Saint Petersburg Academic University, Saint Petersburg National Research Academic University of the Russian Academy of Sciences
  9. Theo M. Luider · Erasmus MC, Erasmus University Rotterdam
  10. Ljiljana Paša-Tolić · Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory
  11. 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

  • T-Bruijn graph top-down de novo sequencing: De novo sequencing from TOP-DOWN spectra, where the whole protein is fragmented rather than tryptic peptides: derives sequence tags and assembles them through a T-Bruijn graph, evaluated on carbonic anhydrase 2 and an alemtuzumab Fab.

Cites (27)

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