title: DISMS2: A flexible algorithm for direct proteome- wide distance calculation of LC-MS/MS runs.
abstract: BACKGROUND
  The classification of samples on a molecular level has manifold applications, from patient classification regarding cancer treatment to phylogenetics for identifying evolutionary relationships between species. Modern methods employ the alignment of DNA or amino acid sequences, mostly not genome-wide but only on selected parts of the genome. Recently proteomics-based approaches have become popular. An established method for the identification of peptides and proteins is liquid chromatography-tandem mass spectrometry (LC-MS/MS). First, protein sequences from MS/MS spectra are identified by means of database searches, given samples with known genome-wide sequence information, then sequence based methods are applied. Alternatively, de novo peptide sequencing algorithms annotate MS/MS spectra and deduce peptide/protein information without a database. A newer approach independent of additional information is to directly compare unidentified tandem mass spectra. The challenge then is to compute the distance between pairwise MS/MS runs consisting of thousands of spectra.
  
  
  METHODS
  We present DISMS2, a new algorithm to calculate proteome-wide distances directly from MS/MS data, extending the algorithm compareMS2, an approach that also uses a spectral comparison pipeline.
  
  
  RESULTS
  Our new more flexible algorithm, DISMS2, allows for the choice of the spectrum distance measure and includes different spectra preprocessing and filtering steps that can be tailored to specific situations by parameter optimization.
  
  
  CONCLUSIONS
  DISMS2 performs well for samples from species with and without database annotation and thus has clear advantages over methods that are purely based on database search.
authors.affiliation: Department of Statistics, TU Dortmund University, Dortmund, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Rieder
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Blank-Landeshammer
authors.affiliation: Leibniz Center for Tropical Marine Ecology (ZMT), Bremen, Germany.
authors.forename: Marleen
authors.initials: M
authors.lastname: Stuhr
authors.affiliation: Biodiversity and Climate Research Centre, Senckenberg Gesellschaft für Naturforschung, Frankfurt, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schell
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Biß
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.
authors.forename: Laxmikanth
authors.initials: L
authors.lastname: Kollipara
authors.affiliation: Leibniz Center for Tropical Marine Ecology (ZMT), Bremen, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Biodiversity and Climate Research Centre, Senckenberg Gesellschaft für Naturforschung, Frankfurt, Germany.|Faculty of Biological Science, Institute for Ecology, Evolution and Diversity, Department of Molecular Ecology, Goethe University, Max-von-Laue-Straße 9, Frankfurt am Main, 60438, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Pfenninger
authors.affiliation: Leibniz Center for Tropical Marine Ecology (ZMT), Bremen, Germany.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Westphal
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany.|Department of Chemistry, College of Physical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom.|Medizinische Fakultät, Medizinisches Proteom-Center (MPC), Ruhr-Universität Bochum, Universitätsstraße 150, Bochum, 44801, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.affiliation: Department of Statistics, TU Dortmund University, Dortmund, Germany. rahnenfuehrer@statistik.tu-dortmund.de.
authors.forename: Jörg
authors.identifier: http://orcid.org/0000-0002-8947-440X
authors.initials: J
authors.lastname: Rahnenführer
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002853:Chromatography, Liquid / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D010455:Peptides / Q000032:analysis*; D020543:Proteome / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010455:Peptides; D020543:Proteome
keywords: Comparison of MS/MS spectra; Distance of LC-MS/MS runs; LC-MS/MS; Mass spectrometry; Peptide identification; Proteomics