title: De novo peptide sequencing and identification with precision mass spectrometry.
abstract: The recent proliferation of novel mass spectrometers such as Fourier transform, QTOF, and OrbiTrap marks a transition into the era of precision mass spectrometry, providing a 2 orders of magnitude boost to the mass resolution, as compared to low-precision ion-trap detectors. We investigate peptide de novo sequencing by precision mass spectrometry and explore some of the differences when compared to analysis of low-precision data. We demonstrate how the dramatically improved performance of de novo sequencing with precision mass spectrometry paves the way for novel approaches to peptide identification that are based on direct sequence lookups, rather than comparisons of spectra to a database. With the direct sequence lookup, it is not only possible to search a database very efficiently, but also to use the database in novel ways, such as searching for products of alternative splicing or products of fusion proteins in cancer. Our de novo sequencing software is available for download at http://peptide.ucsd.edu/.
authors.affiliation: Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California 92093-0404, USA. arf@cs.ucsd.edu
authors.forename: Ari M
authors.initials: AM
authors.lastname: Frank
authors.forename: Mikhail M
authors.initials: MM
authors.lastname: Savitski
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nielsen
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Pevzner
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D019295:Computational Biology / Q000379:methods; D003627:Data Interpretation, Statistical; D030562:Databases, Protein; D005583:Fourier Analysis; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009363:Neoplasm Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011336:Probability; D020539:Sequence Analysis, Protein; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D009363:Neoplasm Proteins; D010455:Peptides