Automated lipid A structure assignment from hierarchical tandem mass spectrometry data
Ying S Ting1, Scott A Shaffer, Jace W Jones
1Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195-7610, USA.
Journal of the American Society for Mass Spectrometry
|April 8, 2011
Summary
A new computational method, the hierarchical tandem mass spectrometry (HiTMS) algorithm, automates lipid A structural analysis from mass spectrometry data. This tool rapidly annotates spectra, aiding experts in identifying lipid A structures across different species.
Area of Science:
- Lipidomics
- Mass Spectrometry
- Computational Biology
Background:
- Electrospray ionization (ESI) coupled with multiple-stage tandem mass spectrometry (MS(n)) is standard for lipid A structural analysis.
- Manual annotation of MS(n) spectra is time-consuming and limits throughput.
Purpose of the Study:
- To develop a rapid, automated computational method for annotating lipid A MS(n) spectra.
- To create a tool that assists experts in interpreting complex lipid A structural data.
Main Methods:
- Developed the hierarchical tandem mass spectrometry (HiTMS) algorithm.
- Utilized species-specific libraries and prior structural knowledge.
- Deciphered signature ions and neutral losses in MS(n) spectra.
- Selected candidate structures by correlating theoretical and acquired spectra.
Main Results:
- HiTMS correctly assigned 85% of lipid A structures in a library of 133 manually annotated *Francisella tularensis subspecies novicida*.
- Achieved a false discovery rate below 0.01.
- Demonstrated cross-species applicability by correctly assigning 85% of *Yersinia pestis* lipid A structures.
Conclusions:
- The HiTMS algorithm provides rapid and accurate annotation of lipid A MS(n) spectra.
- HiTMS serves as an effective first-pass tool to aid expert interpretation.
- The method shows potential for broad application across various bacterial species.
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