title: A systematic framework to derive N-glycan biosynthesis process and the automated construction of glycosylation networks.
abstract: BACKGROUND
  Abnormalities in glycan biosynthesis have been conclusively related to various diseases, whereas the complexity of the glycosylation process has impeded the quantitative analysis of biochemical experimental data for the identification of glycoforms contributing to disease. To overcome this limitation, the automatic construction of glycosylation reaction networks in silico is a critical step.
  
  
  RESULTS
  In this paper, a framework K2014 is developed to automatically construct N-glycosylation networks in MATLAB with the involvement of the 27 most-known enzyme reaction rules of 22 enzymes, as an extension of previous model KB2005. A toolbox named Glycosylation Network Analysis Toolbox (GNAT) is applied to define network properties systematically, including linkages, stereochemical specificity and reaction conditions of enzymes. Our network shows a strong ability to predict a wider range of glycans produced by the enzymes encountered in the Golgi Apparatus in human cell expression systems.
  
  
  CONCLUSIONS
  Our results demonstrate a better understanding of the underlying glycosylation process and the potential of systems glycobiology tools for analyzing conventional biochemical or mass spectrometry-based experimental data quantitatively in a more realistic and practical way.
authors.affiliation: Department of Mathematics, The University of Hong Kong, Hong Kong, 999077, China. whou@connect.hku.hk.
authors.forename: Wenpin
authors.initials: W
authors.lastname: Hou
authors.affiliation: Hematology Oncology Division, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Faculty of Science and Engineering, Soka University, Tokyo, 192-8577, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Mathematics, The University of Hong Kong, Hong Kong, 999077, China.
authors.forename: Wai-Ki
authors.initials: WK
authors.lastname: Ching
authors.affiliation: Faculty of Science and Engineering, Soka University, Tokyo, 192-8577, Japan.
authors.forename: Kiyoko F
authors.initials: KF
authors.lastname: Aoki-Kinoshita
mesh_terms: D053898:Biosynthetic Pathways; D003198:Computer Simulation; D054794:Glycomics / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D013058:Mass Spectrometry; D008954:Models, Biological; D011134:Polysaccharides / Q000096:biosynthesis*; D014166:Transferases / Q000378:metabolism
chemical_list: D011134:Polysaccharides; D014166:Transferases; D006867:Hydrolases
keywords: Glycobiology; Glycosylation enzyme activity; Glycosylation reaction networks construction; Mass spectrum; N-glycan