title: Deuteration distribution estimation with improved sequence coverage for HX/MS experiments.
abstract: BACKGROUND
  Time-resolved hydrogen exchange (HX) followed by mass spectrometry (MS) is a key technology for studying protein structure, dynamics and interactions. HX experiments deliver a time-dependent distribution of deuteration levels of peptide sequences of the protein of interest. The robust and complete estimation of this distribution for as many peptide fragments as possible is instrumental to understanding dynamic protein-level HX behavior. Currently, this data interpretation step still is a bottleneck in the overall HX/MS workflow.
  
  
  RESULTS
  We propose HeXicon, a novel algorithmic workflow for automatic deuteration distribution estimation at increased sequence coverage. Based on an L(1)-regularized feature extraction routine, HeXicon extracts the full deuteration distribution, which allows insight into possible bimodal exchange behavior of proteins, rather than just an average deuteration for each time point. Further, it is capable of addressing ill-posed estimation problems, yielding sparse and physically reasonable results. HeXicon makes use of existing peptide sequence information, which is augmented by an inferred list of peptide candidates derived from a known protein sequence. In conjunction with a supervised classification procedure that balances sensitivity and specificity, HeXicon can deliver results with increased sequence coverage.
  
  
  BACKGROUND
  The entire HeXicon workflow has been implemented in C++ and includes a graphical user interface. It is available at http://hci.iwr.uni-heidelberg.de/software.php.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, Germany.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Lou
authors.forename: Marc
authors.initials: M
authors.lastname: Kirchner
authors.forename: Bernhard Y
authors.initials: BY
authors.lastname: Renard
authors.forename: Ullrich
authors.initials: U
authors.lastname: Köthe
authors.forename: Sebastian
authors.initials: S
authors.lastname: Boppel
authors.forename: Christian
authors.initials: C
authors.lastname: Graf
authors.forename: Chung-Tien
authors.initials: CT
authors.lastname: Lee
authors.forename: Judith A J
authors.initials: JA
authors.lastname: Steen
authors.forename: Hanno
authors.initials: H
authors.lastname: Steen
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Mayer
authors.forename: Fred A
authors.initials: FA
authors.lastname: Hamprecht
mesh_terms: D000465:Algorithms; D003903:Deuterium / Q000737:chemistry; D041961:Deuterium Exchange Measurement / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D014584:User-Computer Interface
chemical_list: D011506:Proteins; D003903:Deuterium