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.

de novo sequencing, T-Bruijn graph, top-down mass spectrometry
dx.doi.org/10.1021/pr501244v, hdl.handle.net/1765/88208
Journal of Proteome Research
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Department of Neurology

Vyatkina, K, Wu, S, Dekker, L.J.M, van Duijn, M.M, Liu, X, Tolić, N, … Pevzner, P.A. (2015). De novo sequencing of peptides from top-down tandem mass spectra. Journal of Proteome Research, 14(11), 4450–4462. doi:10.1021/pr501244v