Journal Article

Systems-level modeling of cellular glycosylation reaction networks: O-linked glycan formation on natural selectin ligands

Gang Liu, Dhananjay D. Marathe, Khushi L. Matta and Sriram Neelamegham

in Bioinformatics

Volume 24, issue 23, pages 2740-2747
Published in print December 2008 | ISSN: 1367-4803
Published online October 2008 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btn515
Systems-level modeling of cellular glycosylation reaction networks: O-linked glycan formation on natural selectin ligands

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Motivation: The emerging field of Glycomics requires the development of systems-based modeling strategies to relate glycosyltransferase gene expression and enzyme activity with carbohydrate structure and function.

Results: We describe the application of object oriented programming concepts to define glycans, enzymes, reactions, pathways and compartments for modeling cellular glycosylation reaction networks. These class definitions are combined with current biochemical knowledge to define potential reaction networks that participate in the formation of the sialyl Lewis-X (sLeX) epitope on O-glycans linked to a leukocyte cell-surface glycoprotein, P-selectin Glycoprotein Ligand-1 (PSGL-1). Subset modeling, hierarchical clustering, principal component analysis and adjoint sensitivity analysis are applied to refine the reaction network and to quantify individual glycosyltransferase rate constants. Wet-lab experiments validate estimates from computer modeling. Such analysis predicts that sLeX expression varies directly with sialyltransferase α2,3ST3Gal-IV expression and inversely with α2,3ST3Gal-I/II.

Availability: SBML files for all converged models are available at http://www.eng.buffalo.edu/~neel/bio_reaction_network.html

Contact: neel@eng.buffalo.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  6056 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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