Abstract
Advances in high-throughput techniques have led to the creation of increasing amounts of glycome data. The storage and analysis of this data would benefit greatly from a compact notation for describing glycan structures that can be easily stored and interpreted by computers. Towards this end, we propose a fixed-length alpha-numeric code for representing N-linked glycan structures commonly found in secreted glycoproteins from mammalian cell cultures. This code, GlycoDigit, employs a pre-assigned alpha-numeric index to represent the monosaccharides attached in different branches to the core glycan structure. The present branch-centric representation allows us to visualize the structure while the numerical nature of the code makes it machine readable. In addition, a difference operator can be defined to quantitatively differentiate between glycan structures for further analysis. The usefulness and applicability of GlycoDigit were demonstrated by constructing and visualizing an N-linked glycosylation network.
Similar content being viewed by others
Abbreviations
- CHO:
-
Chinese Hamster ovary
- Gal:
-
Galactose
- GlcNAc:
-
N-Acetylglucosamine
- IUPAC:
-
International Union for Pure and Applied Chemistry
- Man:
-
Mannose
- NeuNAc:
-
N-Acetylneuraminic acid
References
Pérez S, Mulloy B (2005) Prospects for glycoinformatics. Curr Opin Struct Biol 15:517–524
von der Lieth CW (2004) An endorsement to create open databases for analytical data of complex carbohydrates. J Carbohydr Chem 23:277–297
Laine RA (1994) A calculation of all possible oligosaccharide isomers both branched and linear yields 1.05 × 10(12) structures for a reducing hexasaccharide: the Isomer Barrier to development of single-method saccharide sequencing or synthesis systems. Glycobiology 6:759–767
von der Lieth CW, Bohne-Lang A, Lohmann KK, Frank M (2004) Bioinformatics for glycomics: status, methods, requirements and perspectives. Brief Bioinform 5:164–178
Brazma A, Krestyaninova M, Sarkans U (2006) Standards for systems biology. Nat Rev Genet 7:593–605
McNaught AD (1997) Nomenclature of carbohydrates (recommendations 1996). Adv Carbohydr Chem Biochem 52:43–177
Bohne-Lang A, Lang E, Forster T, von der Lieth CW (2001) LINUCS: linear notation for unique description of carbohydrate sequences. Carbohydr Res 336:1–11
Banin E, Neuberger Y, Altshuler Y, Halevi A, Inbar O, Nir D, Dukler A (2002) A novel linear code nomenclature for complex carbohydrates. Trends Glycosci Glycotechnol 14:127–137
Sahoo SS, Thomas C, Sheth A, Henson C, York WS (2005) GLYDE-an expressive XML standard for the representation of glycan structure. Carbohydr Res 340:2802–2807
Kikuchi N, Kameyama A, Nakaya S, Ito H, Sato T, Shikanai T, Takahashi Y, Narimatsu H (2005) The carbohydrate sequence markup language (CabosML): an XML description of carbohydrate structures. Bioinformatics 21:1717–1718
Toukach P, Joshi HJ, Ranzinger R, Knirel Y, von der Lieth CW (2007) Sharing of worldwide distributed carbohydrate-related digital resources: online connection of the bacterial carbohydrate structure database and GLYCOSCIENCES.de. Nucleic Acids Res 35:D280–286
Varki A et al (eds) (1999) Essentials of glycobiology. Cold Spring Harbor Laboratory Press, New York
Campbell C, Stanley P (1984) A dominant mutation to ricin resistance in Chinese hamster ovary cells induces UDP-GlcNAc:glycopeptide beta-4-N-acetylglucosaminyltransferase III activity. J Biol Chem 259:13370–13378
Sburlati AR, Umana P, Prati EG, Bailey JE (1998) Synthesis of bisected glycoforms of recombinant IFN-beta by over-expression of beta-1,4-N-acetylglucosaminyltransferase III in Chinese hamster ovary cells. Biotechnol Prog 14:189–192
Umana P, Jean-Mairet J, Moudry R, Amstutz H, Bailey JE (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat Biotechnol 17:176–180
Baker KN, Rendall MH, Hills AE, Hoare M, Freedman RB, James DC (2001) Metabolic control of recombinant protein N-glycan processing in NS0 and CHO cells. Biotechnol Bioeng 73:188–202
Irie A, Koyama S, Kozutsumi Y, Kawasaki T, Suzuki A (1998) The molecular basis for the absence of N-glycolylneuraminic acid in humans. J Biol Chem 273:15866–15871
Butler M (2006) Optimisation of the cellular metabolism of glycosylation for recombinant proteins produced by mammalian cell systems. Cytotechnology 50:57–76
Jenkins N, Parekh RB, James DC (1996) Getting the glycosylation right: implications for the biotechnology industry. Nat Biotechnol 14:975–981
Ma B, Simala-Grant JL, Taylor DE (2006) Fucosylation in prokaryotes and eukaryotes. Glycobiology 16:158R–184R
Sasaki H, Bothner B, Dell A, Fukuda M (1987) Carbohydrate structure of erythropoietin expressed in Chinese hamster ovary cells by a human erythropoietin cDNA. J Biol Chem 262:12059–12076
Thomas LJ, Panneerselvam K, Beattie DT, Picard MD, Xu B, Rittershaus CW, Marsh HC Jr, Hammond RA, Qian J, Stevenson T, Zopf D, Bayer RJ (2004) Production of a complement inhibitor possessing sialyl Lewis X moieties by in vitro glycosylation technology. Glycobiology 14:883–893
Barrabés S, Pagès-Pons L, Radcliffe CM, Tabarès G, Fort E, Royle L, Harvey DJ, Moenner M, Dwek RA, Rudd PM, De Llorens R, Peracaula R (2007) Glycosylation of serum ribonuclease 1 indicates a major endothelial origin and reveals an increase in core fucosylation in pancreatic cancer. Glycobiology 17:388–400
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410
Aoki KF, Yamaguchi A, Ueda N, Akutsu T, Mamitsuka H, Goto S, Kanehisa M (2004) KCaM (KEGG Carbohydrate Matcher): a software tool for analyzing the structures of carbohydrate sugar chains. Nucleic Acids Res 32:W267–W272
Aoki KF, Mamitsuka H, Akutsu T, Kanehisa M (2005) A score matrix to reveal the hidden links in glycans. Bioinformatics 21:1457–1463
Hossler P, Goh LT, Lee MM, Hu WS (2006) GlycoVis: visualizing glycan distribution in the protein N-glycosylation pathway in mammalian cells. Biotechnol Bioeng 95:946–960
Hashimoto K, Goto S, Kawano S, Aoki-Kinoshita KF, Ueda N, Hamajima M, Kawasaki T, Kanehisa M (2006) KEGG as a glycome informatics resource. Glycobiology 16:63R–70R
Lutteke T, Bohne-Lang A, Loss A, Goetz T, Frank M, von der Lieth CW (2006) GLYCOSCIENCES.de: an Internet portal to support glycomics and glycobiology research. Glycobiology 16:71R–81R
Raman R, Venkataraman M, Ramakrishnan S, Lang W, Raguram S, Sasisekharan R (2006) Advancing glycomics: implementation strategies at the consortium for functional glycomics. Glycobiology 16:82R–90R
Hossler P, Mulukutla BC, Hu WS (2007) Systems analysis of N-glycan processing in mammalian cells. PLoS ONE 2(8):e713
Krambeck FJ, Betenbaugh MJ (2005) A mathematical model of N-linked glycosylation. Biotechnol Bioeng 92:711–728
Umana P, Bailey JE (1997) A mathematical model of N-linked glycoform biosynthesis. Biotechnol Bioeng 55:890–908
Bertozzi CR, Kiessling LL (2001) Carbohydrates and glycobiology review: chemical glycobiology. Science 291:2357–2364
Acknowledgments
This work was supported by the Biomedical Research Council of A*STAR (Agency for Science, Technology and Research), Singapore. The authors would like to thank Dr. Niki Wong and Mr. Robin J. Philp for their valuable comments and suggestions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yusufi, F.N.K., Park, W., Lee, M.M. et al. An alpha-numeric code for representing N-linked glycan structures in secreted glycoproteins. Bioprocess Biosyst Eng 32, 97–107 (2009). https://doi.org/10.1007/s00449-008-0226-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00449-008-0226-4