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Hexicon 2: Automated Processing of Hydrogen-Deuterium Exchange Mass Spectrometry Data with Improved Deuteration Distribution Estimation

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    Research Article

    Hexicon 2: Automated Processing of Hydrogen-Deuterium Exchange Mass Spectrometry Data with Improved Deuteration Distribution Estimation
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    • Robert Lindner
      Robert Lindner
      Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Heidelberg, Germany
      More by Robert Lindner
    • Xinghua Lou
      Xinghua Lou
      Heidelberg Collaboratory for Image Processing (HCI), University of Heidelberg, Heidelberg, Germany
      More by Xinghua Lou
    • Jochen Reinstein
      Jochen Reinstein
      Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Heidelberg, Germany
      More by Jochen Reinstein
    • Robert L Shoeman
      Robert L Shoeman
      Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Heidelberg, Germany
      More by Robert L Shoeman
    • Fred A Hamprecht
      Fred A Hamprecht
      Heidelberg Collaboratory for Image Processing (HCI), University of Heidelberg, Heidelberg, Germany
      More by Fred A Hamprecht
    • Andreas Winkler
      Andreas Winkler
      Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Heidelberg, Germany
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    Journal of The American Society for Mass Spectrometry

    Cite this: J. Am. Soc. Mass Spectrom. 2014, 25, 6, 1018–1028
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    https://doi.org/10.1007/s13361-014-0850-y
    Published March 28, 2014
    Copyright © 2014 © The Author(s) 2014
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    Abstract

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    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.

    Copyright © 2014 © The Author(s) 2014

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    Journal of The American Society for Mass Spectrometry

    Cite this: J. Am. Soc. Mass Spectrom. 2014, 25, 6, 1018–1028
    Click to copy citationCitation copied!
    https://doi.org/10.1007/s13361-014-0850-y
    Published March 28, 2014
    Copyright © 2014 © The Author(s) 2014
    Request reuse permissions

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