De Novo Sequencing of Peptides from Top-Down Tandem Mass Spectra.
J Proteome Res
; 14(11): 4450-62, 2015 Nov 06.
Article
in En
| MEDLINE
| ID: mdl-26412692
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Peptides
/
Algorithms
/
Sequence Analysis, Protein
/
Proteomics
/
Tandem Mass Spectrometry
Limits:
Animals
/
Humans
Language:
En
Journal:
J Proteome Res
Journal subject:
BIOQUIMICA
Year:
2015
Type:
Article
Affiliation country:
RUSSIA