title: A Multivariate Mixture Model to Estimate the Accuracy of Glycosaminoglycan Identifications Made by Tandem Mass Spectrometry (MS/MS) and Database Search.
abstract: We present a statistical model to estimate the accuracy of derivatized heparin and heparan sulfate (HS) glycosaminoglycan (GAG) assignments to tandem mass (MS/MS) spectra made by the first published database search application, GAG-ID. Employing a multivariate expectation-maximization algorithm, this statistical model distinguishes correct from ambiguous and incorrect database search results when computing the probability that heparin/HS GAG assignments to spectra are correct based upon database search scores. Using GAG-ID search results for spectra generated from a defined mixture of 21 synthesized tetrasaccharide sequences as well as seven spectra of longer defined oligosaccharides, we demonstrate that the computed probabilities are accurate and have high power to discriminate between correctly, ambiguously, and incorrectly assigned heparin/HS GAGs. This analysis makes it possible to filter large MS/MS database search results with predictable false identification error rates.
authors.affiliation: From the ‡Complex Carbohydrate Research Center.|§Institute of Bioinformatics.
authors.forename: Yulun
authors.initials: Y
authors.lastname: Chiu
authors.affiliation: ¶Department of Statistics, University of Georgia, Athens, GA, 30602.
authors.forename: Paul
authors.initials: P
authors.lastname: Schliekelman
authors.affiliation: From the ‡Complex Carbohydrate Research Center.
authors.forename: Ron
authors.initials: R
authors.lastname: Orlando
authors.affiliation: ‖Department of BioMolecular Sciences, University of Mississippi, University, MS, 38677 jsharp@olemiss.edu.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Sharp
mesh_terms: D000465:Algorithms; D030562:Databases, Protein; D006025:Glycosaminoglycans / Q000032:analysis*; D006493:Heparin / Q000032:analysis; D006497:Heparan Sulfate / Q000032:analysis; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D010455:Peptides