title: Improved cell typing by charge-state deconvolution of matrix-assisted laser desorption/ionization mass spectra.
abstract: Robust, specific, and rapid identification of toxic strains of bacteria and viruses, to guide the mitigation of their adverse health effects and optimum implementation of other response actions, remains a major analytical challenge. This need has driven the development of methods for classification of microorganisms using mass spectrometry, particularly matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), that allows high-throughput analyses with minimum sample preparation. We describe a novel approach to cell typing based on pattern recognition of MALDI mass spectra, which involves charge-state deconvolution in conjunction with a new correlation analysis procedure. The method is applicable to both prokaryotic and eukaryotic cells. Charge-state deconvolution improves the quantitative reproducibility of spectra because multiply charged ions resulting from the same biomarker attaching a different number of protons are recognized and their abundances are combined. This allows a clearer distinction of bacterial strains or of cancerous and normal liver cells. Improved class distinction provided by charge-state deconvolution was demonstrated by cluster spacing on canonical variate score charts and by correlation analyses. Deconvolution may enhance detection of early disease state or therapy progress markers in various tissues analyzed by MALDI-MS.
authors.affiliation: National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079, USA. jon.wilkes@fda.hhs.gov
authors.forename: Jon G
authors.initials: JG
authors.lastname: Wilkes
authors.forename: Dan A
authors.initials: DA
authors.lastname: Buzatu
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Dare
authors.forename: Yvonne P
authors.initials: YP
authors.lastname: Dragan
authors.forename: M Paul
authors.initials: MP
authors.lastname: Chiarelli
authors.forename: Ricky D
authors.initials: RD
authors.lastname: Holland
authors.forename: Michael
authors.initials: M
authors.lastname: Beaudoin
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Heinze
authors.forename: Rajesh
authors.initials: R
authors.lastname: Nayak
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Shvartsburg
mesh_terms: D000465:Algorithms; D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000145:classification; D002477:Cells / Q000737:chemistry / Q000145:classification*; D002954:Citrobacter / Q000737:chemistry / Q000145:classification; D005057:Eukaryotic Cells / Q000737:chemistry / Q000145:classification; D008099:Liver / Q000737:chemistry / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019779:Salmonella enterica / Q000737:chemistry / Q000145:classification; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods* / Q000706:statistics & numerical data