Investigating the use of derivative peaks in the alignment of LC-MS data.
Joe Wandy, Rónán Daly, Rainer Breitling & Simon Rogers
Liquid chromatography (LC), followed by mass spectrometry (MS), has become one of the most commonly used tools in untargeted metabolomic studies. In almost all experimental designs, it is necessary to compare chromatograms across biological or technical replicates and across sample groups. Central to this step is the alignment of peaks across various chromatograms.
Alignment of peaks is a challenging problem due to missing data (peaks not observed in some chromatograms) and the potentially non-linear shifts in retention time between chromatograms. Existing tools use the information for peaks, without taking into account dependencies between peaks. But fragment and isotope peaks derived from the same metabolite should show the same chromatographic behaviour, and combining the information from their chromatograms (using e.g. chromatographic peak shape) could potentially be used to improve alignment quality.
In this work, we investigate ways to incorporate the information from derivative peaks into the alignment process, using a graph-based approach. In particular, we investigate whether concordant alignments within groups of derivative peaks can result in increased confidence about the quality of those alignments. Based on experiments with real metabolomic data , we find that using this approach allows us to explicitly trade recall for precision when producing a final set of alignments.
 Lange, E., Tautenhahn, R., Neumann, S., & Gröpl, C. (2008). Critical assessment of alignment procedures for LC-MS proteomics and metabolomics measurements. BMC Bioinformatics, 9, 375. doi:10.1186/1471-2105-9-375
To be presented in Mathematical and Statistical Aspects of Molecular Biology, 23rd annual MASAMB workshop.