### Abstract

Effective representation and characterization of biosynthetic pathways of glycosylation can be facilitated by mathematical modeling. This paper describes the expansion of a previously developed detailed model for N-linked glycosylation with the further application of the model to analyze MALDI-TOF mass spectra of human N-glycans in terms of underlying cellular enzyme activities. The glycosylation reaction network is automatically generated by the model, based on the reaction specificities of the glycosylation enzymes. The use of a molecular mass cutoff and a network pruning method typically limits the model size to about 10,000 glycan structures. This allows prediction of the complete glycan profile and its abundances for any set of assumed enzyme concentrations and reaction rate parameters. A synthetic mass spectrum from model-calculated glycan profiles is obtained and enzyme concentrations are adjusted to bring the theoretically calculated mass spectrum into agreement with experiment. The result of this process is a complete characterization of a measured glycan mass spectrum containing hundreds of masses in terms of the activities of 19 enzymes. In addition, a complete annotation of the mass spectrum in terms of glycan structure is produced, including the proportions of isomers within each peak. The method was applied to mass spectrometric data of normal human monocytes and monocytic leukemia (THP1) cells to derive glycosyltransferase activity changes underlying the differences in glycan structure between the normal and diseased cells. Model predictions could lead to a better understanding of the changes associated with disease states, identification of disease-associated biomarkers, and bioengineered glycan modifications.

Original language | English (US) |
---|---|

Pages (from-to) | 1163-1175 |

Number of pages | 13 |

Journal | Glycobiology |

Volume | 19 |

Issue number | 11 |

DOIs | |

State | Published - 2009 |

### Fingerprint

### Keywords

- Automatic glycan annotation
- Glycosylation enzyme activity
- Mass spectrum
- Mathematical model
- Monocytic leukemia

### ASJC Scopus subject areas

- Biochemistry

### Cite this

*Glycobiology*,

*19*(11), 1163-1175. https://doi.org/10.1093/glycob/cwp081

**A mathematical model to derive N-glycan structures and cellular enzyme activities from mass spectrometric data.** / Krambeck, Frederick J.; Bennun, Sandra V.; Narang, Someet; Choi, Sean; Yarema, Kevin J; Betenbaugh, Michael J.

Research output: Contribution to journal › Article

*Glycobiology*, vol. 19, no. 11, pp. 1163-1175. https://doi.org/10.1093/glycob/cwp081

}

TY - JOUR

T1 - A mathematical model to derive N-glycan structures and cellular enzyme activities from mass spectrometric data

AU - Krambeck, Frederick J.

AU - Bennun, Sandra V.

AU - Narang, Someet

AU - Choi, Sean

AU - Yarema, Kevin J

AU - Betenbaugh, Michael J.

PY - 2009

Y1 - 2009

N2 - Effective representation and characterization of biosynthetic pathways of glycosylation can be facilitated by mathematical modeling. This paper describes the expansion of a previously developed detailed model for N-linked glycosylation with the further application of the model to analyze MALDI-TOF mass spectra of human N-glycans in terms of underlying cellular enzyme activities. The glycosylation reaction network is automatically generated by the model, based on the reaction specificities of the glycosylation enzymes. The use of a molecular mass cutoff and a network pruning method typically limits the model size to about 10,000 glycan structures. This allows prediction of the complete glycan profile and its abundances for any set of assumed enzyme concentrations and reaction rate parameters. A synthetic mass spectrum from model-calculated glycan profiles is obtained and enzyme concentrations are adjusted to bring the theoretically calculated mass spectrum into agreement with experiment. The result of this process is a complete characterization of a measured glycan mass spectrum containing hundreds of masses in terms of the activities of 19 enzymes. In addition, a complete annotation of the mass spectrum in terms of glycan structure is produced, including the proportions of isomers within each peak. The method was applied to mass spectrometric data of normal human monocytes and monocytic leukemia (THP1) cells to derive glycosyltransferase activity changes underlying the differences in glycan structure between the normal and diseased cells. Model predictions could lead to a better understanding of the changes associated with disease states, identification of disease-associated biomarkers, and bioengineered glycan modifications.

AB - Effective representation and characterization of biosynthetic pathways of glycosylation can be facilitated by mathematical modeling. This paper describes the expansion of a previously developed detailed model for N-linked glycosylation with the further application of the model to analyze MALDI-TOF mass spectra of human N-glycans in terms of underlying cellular enzyme activities. The glycosylation reaction network is automatically generated by the model, based on the reaction specificities of the glycosylation enzymes. The use of a molecular mass cutoff and a network pruning method typically limits the model size to about 10,000 glycan structures. This allows prediction of the complete glycan profile and its abundances for any set of assumed enzyme concentrations and reaction rate parameters. A synthetic mass spectrum from model-calculated glycan profiles is obtained and enzyme concentrations are adjusted to bring the theoretically calculated mass spectrum into agreement with experiment. The result of this process is a complete characterization of a measured glycan mass spectrum containing hundreds of masses in terms of the activities of 19 enzymes. In addition, a complete annotation of the mass spectrum in terms of glycan structure is produced, including the proportions of isomers within each peak. The method was applied to mass spectrometric data of normal human monocytes and monocytic leukemia (THP1) cells to derive glycosyltransferase activity changes underlying the differences in glycan structure between the normal and diseased cells. Model predictions could lead to a better understanding of the changes associated with disease states, identification of disease-associated biomarkers, and bioengineered glycan modifications.

KW - Automatic glycan annotation

KW - Glycosylation enzyme activity

KW - Mass spectrum

KW - Mathematical model

KW - Monocytic leukemia

UR - http://www.scopus.com/inward/record.url?scp=70349978981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349978981&partnerID=8YFLogxK

U2 - 10.1093/glycob/cwp081

DO - 10.1093/glycob/cwp081

M3 - Article

C2 - 19506293

AN - SCOPUS:70349978981

VL - 19

SP - 1163

EP - 1175

JO - Glycobiology

JF - Glycobiology

SN - 0959-6658

IS - 11

ER -