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

K Vyatkina, S Wu, Lennard Dekker, Martijn van Duijn, XW Liu, N Tolic, M Dvorkin, S Alexandrova, Theo Luider, L Pasa-Tolic, PA Pevzner

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28 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)4450-4462
Number of pages13
JournalJournal of Proteome Research
Issue number11
Publication statusPublished - 2015

Research programs

  • EMC MM-03-44-06

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