Chromatographic alignment of LC-MS and LC-MS/MS datasets by genetic algorithm feature extraction

  • Magnus Palmblad
  • Davinia J. Mills
  • Laurence V. Bindschedler
  • Rainer Cramer


Liquid chromatography-mass spectrometry (LC-MS) datasets can be compared or combined following chromatographic alignment. Here we describe a simple solution to the specific problem of aligning one LC-MS dataset and one LC-MS/MS dataset, acquired on separate instruments from an enzymatic digest of a protein mixture, using feature extraction and a genetic algorithm. First, the LC-MS dataset is searched within a few ppm of the calculated theoretical masses of peptides confidently identified by LC-MS/MS. A piecewise linear function is then fitted to these matched peptides using a genetic algorithm with a fitness function that is insensitive to incorrect matches but sufficiently flexible to adapt to the discrete shifts common when comparing LC datasets. We demonstrate the utility of this method by aligning ion trap LC-MS/MS data with accurate LC-MS data from an FTICR mass spectrometer and show how hybrid datasets can improve peptide and protein identification by combining the speed of the ion trap with the mass accuracy of the FTICR, similar to using a hybrid ion trap-FTICR instrument. We also show that the high resolving power of FTICR can improve precision and linear dynamic range in quantitative proteomics. The alignment software, msalign, is freely available as open source.


Piecewise Linear Function Breakdown Point FTICR Mass Spectrometer Mascot Generic Format Hybrid Dataset 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

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Supplementary material, approximately 1156 KB.


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Copyright information

© American Society for Mass Spectrometry 2007

Authors and Affiliations

  • Magnus Palmblad
    • 1
  • Davinia J. Mills
    • 1
  • Laurence V. Bindschedler
    • 1
  • Rainer Cramer
    • 1
    • 2
  1. 1.The BioCentreThe University of ReadingWhiteknights, ReadingUnited Kingdom
  2. 2.Department of ChemistryThe University of ReadingReadingUnited Kingdom

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