title: Automated lipid A structure assignment from hierarchical tandem mass spectrometry data.
abstract: Infusion-based electrospray ionization (ESI) coupled to multiple-stage tandem mass spectrometry (MS(n)) 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(n) 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(n) 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(n ) 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(n) 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(n) 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.
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Box 357610, Seattle, WA 98195-7610, USA.
authors.forename: Ying S
authors.initials: YS
authors.lastname: Ting
authors.forename: Scott A
authors.initials: SA
authors.lastname: Shaffer
authors.forename: Jace W
authors.initials: JW
authors.lastname: Jones
authors.forename: Wailap V
authors.initials: WV
authors.lastname: Ng
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D016208:Databases, Factual; D005604:Francisella tularensis / Q000737:chemistry; D008050:Lipid A / Q000737:chemistry* / Q000145:classification; D013045:Species Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015010:Yersinia pestis / Q000737:chemistry
chemical_list: D008050:Lipid A