title: Isotope pattern deconvolution for peptide mass spectrometry by non-negative least squares/least absolute deviation template matching.
abstract: BACKGROUND
  The robust identification of isotope patterns originating from peptides being analyzed through mass spectrometry (MS) is often significantly hampered by noise artifacts and the interference of overlapping patterns arising e.g. from post-translational modifications. As the classification of the recorded data points into either 'noise' or 'signal' lies at the very root of essentially every proteomic application, the quality of the automated processing of mass spectra can significantly influence the way the data might be interpreted within a given biological context.
  
  
  RESULTS
  We propose non-negative least squares/non-negative least absolute deviation regression to fit a raw spectrum by templates imitating isotope patterns. In a carefully designed validation scheme, we show that the method exhibits excellent performance in pattern picking. It is demonstrated that the method is able to disentangle complicated overlaps of patterns.
  
  
  CONCLUSIONS
  We find that regularization is not necessary to prevent overfitting and that thresholding is an effective and user-friendly way to perform feature selection. The proposed method avoids problems inherent in regularization-based approaches, comes with a set of well-interpretable parameters whose default configuration is shown to generalize well without the need for fine-tuning, and is applicable to spectra of different platforms. The R package IPPD implements the method and is available from the Bioconductor platform (http://bioconductor.fhcrc.org/help/bioc-views/devel/bioc/html/IPPD.html).
authors.affiliation: Department of Computer Science, Saarland University, Saarbrücken, Germany. ms@cs.uni-saarland.de
authors.forename: Martin
authors.initials: M
authors.lastname: Slawski
authors.forename: Rene
authors.initials: R
authors.lastname: Hussong
authors.forename: Andreas
authors.initials: A
authors.lastname: Tholey
authors.forename: Thomas
authors.initials: T
authors.lastname: Jakoby
authors.forename: Barbara
authors.initials: B
authors.lastname: Gregorius
authors.forename: Andreas
authors.initials: A
authors.lastname: Hildebrandt
authors.forename: Matthias
authors.initials: M
authors.lastname: Hein
mesh_terms: D000465:Algorithms; D016477:Artifacts; D006801:Humans; D007554:Isotopes / Q000032:analysis / Q000737:chemistry*; D016018:Least-Squares Analysis; D013058:Mass Spectrometry / Q000379:methods*; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*
chemical_list: D007554:Isotopes; D010455:Peptides