Retention Time Alignment of LC/MS Data by a Divide-and-Conquer Algorithm

• Published in: Journal of the American Society for Mass Spectrometry Vol. 23; no. 4; pp. 764 - 772
• Main Author: Zhang, Zhongqi
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.04.2012; Elsevier; Springer Nature B.V
• Subjects: Algorithms; Alignment; Analytical Chemistry; Analytical, structural and metabolic biochemistry; Automation; Bioinformatics; Biological and medical sciences; Biotechnology; Chemistry; Chemistry and Materials Science; Chromatography, Liquid - methods; Databases, Factual; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods; Ions - chemistry; Iterative algorithms; Liquid chromatography; Mass spectrometry; Mass Spectrometry - methods; Metabolomics - methods; Organic Chemistry; Other biological molecules; Proteins; Proteins - chemistry; Proteomics; Proteomics - methods; Research Article; Retention; Metabolomics; Data analysis; Multiple samples; Comparison; Proteomics; Iterative; Pairwise; Quantitation; Chemical analysis; Peptides; Metabolite; Coupled method; Chromatographic retention; HPLC chromatography; Iterative method; Retention time; Algorithm; Protein; Alignment; Peptide fragment; Mass spectrometry; Comparative study; Divide and conquer method; Quantitative analysis
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1007/s13361-011-0334-2

Liquid chromatography-mass spectrometry (LC/MS) has become the method of choice for characterizing complex mixtures. These analyses often involve quantitative comparison of components in multiple samples. To achieve automated sample comparison, the components of interest must be detected and identified, and their retention times aligned and peak areas calculated. This article describes a simple pairwise iterative retention time alignment algorithm, based on the divide-and-conquer approach, for alignment of ion features detected in LC/MS experiments. In this iterative algorithm, ion features in the sample run are first aligned with features in the reference run by applying a single constant shift of retention time. The sample chromatogram is then divided into two shorter chromatograms, which are aligned to the reference chromatogram the same way. Each shorter chromatogram is further divided into even shorter chromatograms. This process continues until each chromatogram is sufficiently narrow so that ion features within it have a similar retention time shift. In six pairwise LC/MS alignment examples containing a total of 6507 confirmed true corresponding feature pairs with retention time shifts up to five peak widths, the algorithm successfully aligned these features with an error rate of 0.2%. The alignment algorithm is demonstrated to be fast, robust, fully automatic, and superior to other algorithms. After alignment and gap-filling of detected ion features, their abundances can be tabulated for direct comparison between samples.