title: De Novo Sequencing of Peptides from Top-Down Tandem Mass Spectra.
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.affiliation: Algorithmic Biology Laboratory, Saint Petersburg Academic University , 8/3 Khlopina Str, Saint Petersburg 194021, Russia.|Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University , 7-9 Universitetskaya nab., Saint Petersburg 199034, Russia.
authors.forename: Kira
authors.initials: K
authors.lastname: Vyatkina
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , 101 Stephenson Pkwy, Norman, Oklahoma 73019, United States.
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Neurology, Erasmus University Medical Center , Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Lennard J M
authors.initials: LJ
authors.lastname: Dekker
authors.affiliation: Department of Neurology, Erasmus University Medical Center , Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Martijn M
authors.initials: MM
authors.lastname: VanDuijn
authors.affiliation: Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis , 535 West Michigan Street, IT 475, Indianapolis, Indiana 46202, United States.|Center for Computational Biology and Bioinformatics, Indiana University School of Medicine , 410 West 10th Street, Suite 5000, Indianapolis, Indiana 46202, United States.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory , Richland, Washington 99352, United States.
authors.forename: Nikola
authors.initials: N
authors.lastname: Tolić
authors.affiliation: Algorithmic Biology Laboratory, Saint Petersburg Academic University , 8/3 Khlopina Str, Saint Petersburg 194021, Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Dvorkin
authors.affiliation: Algorithmic Biology Laboratory, Saint Petersburg Academic University , 8/3 Khlopina Str, Saint Petersburg 194021, Russia.
authors.forename: Sonya
authors.initials: S
authors.lastname: Alexandrova
authors.affiliation: Department of Neurology, Erasmus University Medical Center , Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
authors.affiliation: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory , Richland, Washington 99352, United States.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Paša-Tolić
authors.affiliation: Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University , 7-9 Universitetskaya nab., Saint Petersburg 199034, Russia.|Department of Computer Science and Engineering, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Pevzner
mesh_terms: D000074323:Alemtuzumab; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry; D024402:Carbonic Anhydrase II / Q000737:chemistry; D002417:Cattle; D030562:Databases, Protein; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification*; D040901:Proteomics / Q000379:methods / Q000706:statistics & numerical data*; D020539:Sequence Analysis, Protein / Q000706:statistics & numerical data*; D013194:Staining and Labeling / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000706:statistics & numerical data*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D000074323:Alemtuzumab; D024402:Carbonic Anhydrase II
keywords: T-Bruijn graph; de novo sequencing; top-down mass spectrometry