De Novo Sequencing of Peptides from Top-Down Tandem Mass Spectra
peer-reviewed · Journal of Proteome Research · 2015
| 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 | 3.48 |
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.
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.