Automated Lipid A Structure Assignment from Hierarchical Tandem Mass Spectrometry Data |
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Authors: | Ying S Ting Scott A Shaffer Jace W Jones Wailap V Ng Robert K Ernst David R Goodlett |
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Institution: | (1) Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195-7610, USA;(2) Present address: Jones Environmental, Inc., Fullerton, CA, USA;(3) Department of Biotechnology and Laboratory Science in Medicine, Institute of Biotechnology in Medicine, Institute of Biomedical Informatics, and Center for Systems and Synthetic Biology, National Yang Ming University, Taipei, Taiwan;(4) Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, USA;(5) Present address: University of Massachusetts, Medical School, Worcester, MA, USA; |
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Abstract: | Infusion-based electrospray ionization (ESI) coupled to multiple-stage tandem mass spectrometry (MS
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) is a standard methodology for investigating lipid A structural diversity (Shaffer et al. J. Am. Soc. Mass. Spectrom. 18(6),
1080–1092, 2007). Annotation of these MS
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spectra, however, has remained a manual, expert-driven process. In order to keep up with the data acquisition rates of modern
instruments, we devised a computational method to annotate lipid A MS
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spectra rapidly and automatically, which we refer to as hierarchical tandem mass spectrometry (HiTMS) algorithm. As a first-pass
tool, HiTMS aids expert interpretation of lipid A MS
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data by providing the analyst with a set of candidate structures that may then be confirmed or rejected. HiTMS deciphers
the signature ions (e.g., A-, Y-, and Z-type ions) and neutral losses of MS
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spectra using a species-specific library based on general prior structural knowledge of the given lipid A species under investigation.
Candidates are selected by calculating the correlation between theoretical and acquired MS
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spectra. At a false discovery rate of less than 0.01, HiTMS correctly assigned 85% of the structures in a library of 133
manually annotated Francisella tularensis subspecies novicida lipid A structures. Additionally, HiTMS correctly assigned 85% of the structures in a smaller library of lipid A species
from Yersinia pestis demonstrating that it may be used across species. |
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