Feature Based Retention Time Alignment for Improved HDX MS Analysis

Application Note


An algorithm for retention time alignment of mass shifted hydrogen-deuterium exchange (HDX) data based on an iterative distance minimization procedure is described. The algorithm performs pairwise comparisons in an iterative fashion between a list of features from a reference file and a file to be time aligned to calculate a retention time mapping function. Features are characterized by their charge, retention time and mass of the monoisotopic peak. The algorithm is able to align datasets with mass shifted features, which is a prerequisite for aligning hydrogen-deuterium exchange mass spectrometry datasets. Confidence assignments from the fully automated processing of a commercial HDX software package are shown to benefit significantly from retention time alignment prior to extraction of deuterium incorporation values.

Key words

Hydrogen deuterium exchange Chromatographic alignment Retention time correction Isotopic cluster Fitting Mass spectrometry 

Supplementary material

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  1. 1.
    Zhang, Z.M., Chen, S., Liang, Y.Z.: Peak alignment using wavelet pattern matching and differential evolution. Talanta 83, 1108–1117 (2011)CrossRefGoogle Scholar
  2. 2.
    Tomasi, G., van der Berg, F., Andersson, C.: Correlation optimized warping and dynamic time warping as preprocessing methods for chromatographic data. J. Chemometr. 18, 231–241 (2004)CrossRefGoogle Scholar
  3. 3.
    Ahmad, I., Suits, F., Hoekman, B., Swertz, M.A., Byelas, H., Dijkstra, M., Hooft, R., Katsubo, D., van Breukelen, B., Bischoff, R., Horvatovich, P.: A high-throughput processing service for retention time alignment of complex proteomics and metabolomics LC-MS data. Bioinformatics 27, 1176–1178 (2011)CrossRefGoogle Scholar
  4. 4.
    Hoffmann, N., Stoye, J.: ChromA: Signal-based retention time alignment for chromatography-mass spectrometry data. Bioinformatics 25, 2080–2081 (2009)CrossRefGoogle Scholar
  5. 5.
    Lommen, A.: MetAlign: Interface-driven, versatile metabolomics tool for hyphenated full-scan mass spectrometry data preprocessing. Anal. Chem. 81, 3079–3086 (2009)CrossRefGoogle Scholar
  6. 6.
    Wang, S.Y., Ho, T.J., Kuo, C.H., Tseng, Y.J.: Chromaligner: A web server for chromatogram alignment. Bioinformatics 26, 2338–2339 (2010)CrossRefGoogle Scholar
  7. 7.
    Konermann, L., Pan, J., Liu, Y.H.: Hydrogen exchange mass spectrometry for studying protein structure and dynamics. Chem. Soc. Rev. 40, 1224–1234 (2011)CrossRefGoogle Scholar
  8. 8.
    Center, S.P.: Software:ReAdW. (2012); Available at: http://tools.proteomecenter.org/wiki/index.php?title=Software:ReAdW#Current_Version. Accessed September 3, 2012
  9. 9.
    Bellew, M., Coram, M., Fitzgibbon, M., Igra, M., Randolph, T., Wang, P., May, D., Eng, J., Fang, R., Lin, C., Chen, J., Goodlett, D., Whiteaker, J., Paulovich, A., McIntosh, M.: A suite of algorithms for the comprehensive analysis of complex protein mixtures using high-resolution LC-MS. Bioinformatics 22, 1902–1909 (2006)CrossRefGoogle Scholar
  10. 10.
    Chik, J.K., Graaf, J.L.V., Schriemer, D.C.: Quantitating the statistical distribution of deuterium incorporation to extend the utility of H/D exchange MS data. Anal. Chem. 78, 207–214 (2006)CrossRefGoogle Scholar
  11. 11.
    Chalmers, M.J., Busby, S.A., Pascal, B.D., He, Y., Hendrickson, C.L., Marshall, A.G., Griffin, P.R.: Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry. Anal. Chem. 78, 1005–1014 (2006)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2013

Authors and Affiliations

  1. 1.Genomics Institute of the Novartis Research FoundationSan DiegoUSA
  2. 2.OREIRancho Santa FeUSA

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