title: Hexicon 2: automated processing of hydrogen-deuterium exchange mass spectrometry data with improved deuteration distribution estimation.
abstract: Hydrogen-deuterium exchange (HDX) experiments analyzed by mass spectrometry (MS) provide information about the dynamics and the solvent accessibility of protein backbone amide hydrogen atoms. Continuous improvement of MS instrumentation has contributed to the increasing popularity of this method; however, comprehensive automated data analysis is only beginning to mature. We present Hexicon 2, an automated pipeline for data analysis and visualization based on the previously published program Hexicon (Lou et al. 2010). Hexicon 2 employs the sensitive NITPICK peak detection algorithm of its predecessor in a divide-and-conquer strategy and adds new features, such as chromatogram alignment and improved peptide sequence assignment. The unique feature of deuteration distribution estimation was retained in Hexicon 2 and improved using an iterative deconvolution algorithm that is robust even to noisy data. In addition, Hexicon 2 provides a data browser that facilitates quality control and provides convenient access to common data visualization tasks. Analysis of a benchmark dataset demonstrates superior performance of Hexicon 2 compared with its predecessor in terms of deuteration centroid recovery and deuteration distribution estimation. Hexicon 2 greatly reduces data analysis time compared with manual analysis, whereas the increased number of peptides provides redundant coverage of the entire protein sequence. Hexicon 2 is a standalone application available free of charge under http://hx2.mpimf-heidelberg.mpg.de.
authors.affiliation: Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Heidelberg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Lindner
authors.forename: Xinghua
authors.initials: X
authors.lastname: Lou
authors.forename: Jochen
authors.initials: J
authors.lastname: Reinstein
authors.forename: Robert L
authors.initials: RL
authors.lastname: Shoeman
authors.forename: Fred A
authors.initials: FA
authors.lastname: Hamprecht
authors.forename: Andreas
authors.initials: A
authors.lastname: Winkler
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D041961:Deuterium Exchange Measurement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software
chemical_list: D010455:Peptides; D011506:Proteins