Automated interpretation of MS/MS spectra of oligosaccharides - PubMed (original) (raw)

Automated interpretation of MS/MS spectra of oligosaccharides

Haixu Tang et al. Bioinformatics. 2005 Jun.

Abstract

Motivation: The emerging glycomics and glycoproteomics projects aim to characterize all forms of glycoproteins in different tissues and organisms. Tandem mass spectrometry (MS/MS) is the key experimental methodology for high-throughput glycan identification and characterization. Fragmentation of glycans from high energy collision-induced dissociation generates ions from glycosidic as well as internal cleavages. The cross-ring ions resulting from internal cleavages provide additional information that is important to reveal the type of linkage between monosaccharides. This information, however, is not incorporated into the current programs for analyzing glycan mass spectra. As a result, they can rarely distinguish from the mass spectra isomeric oligosaccharides, which have the same saccharide composition but different types of sequences, branches or linkages.

Results: In this paper, we describe a novel algorithm for glycan characterization using MS/MS. This algorithm consists of three steps. First, we develop a scoring scheme to identify potential bond linkages between monosaccharides, based on the appearance pattern of cross-ring ions. Next, we use a dynamic programming algorithm to determine the most probable oligosaccharide structures from the mass spectrum. Finally, we re-evaluate these oligosaccharide structures, taking into account the double fragmentation ions. We also show the preliminary results of testing our algorithm on several MS/MS spectra of oligosaccharides.

Availability: The program GLYCH is available upon request from the authors.

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Figures

Fig. 1.

Fig. 1.

The structure of oligosaccharides. (a) The open (acyclic) form structure of glucose, an epimer of hexose, one of the monosaccharides, i.e. the basic unit of an oligosaccharide. (b) The cyclic form structure of glucose. The carbon atoms in the ring are not shown. (c) A diglucose, consisting of two glucoses forming a 1-4 glycosidic bond. (d) A tetraglucose, consisting of four glucoses with a branching. (e) The symbolic representation of the tetraglucose shown in (d). The numbers show the linkage types.

Fig. 2.

Fig. 2.

The fragmentation patterns of oligosaccharides. (a) The Y/b and Z/C ions are from the glycosidic cleavages. (b) The cross-ring cleavages create X/A ions. (c) Since the middle unit of the triglucose is linked to two other glucoses, some cleavages create fragment ions with small masses that are not close to the corresponding Y/b ions, e.g. 0,4_X_1. These ions will be ignored in our program.

Fig. 3.

Fig. 3.

The PRMs of an oligosacchrides. (a) An oligosaccharide consisting of 12 glucoses. The glucose residues are indexed according to the partial order of nodes of the tree, from leafs to the root. For any two residues ri and rj, if ri is within the subtree rooted by rj, i must be indexed smaller than j.(b) The subtrees rooted by residues _r_3, _r_9, _r_10, _r_11.

Fig. 4.

Fig. 4.

The structures of the oligosaccharides used for testing in this paper.

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