Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway

Benedetti E, Pucic-Bakovic M, Keser T, Wahl A, Hassinen A, Yang JY, Liu L, Trbojevic-Akmacic I, Razdorov G, Stambuk J, Klaric L, Ugrina I, Selman MHJ, Wuhrer M, Rudan I, Polasek O, Hayward C, Grallert H, Strauch K, Peters A, Meitinger T, Gieger C, Vilaj M, Boons GJ, Moremen KW, Ovchinnikova T, Bovin N, Kellokumpu S, Theis FJ, Lauc G, Krumsiek J (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 8

Article Number: 1483

Journal Issue: 1

DOI: 10.1038/s41467-017-01525-0

Abstract

Immunoglobulin G (IgG) is a major effector molecule of the human immune response, and aberrations in IgG glycosylation are linked to various diseases. However, the molecular mechanisms underlying protein glycosylation are still poorly understood. We present a data-driven approach to infer reactions in the IgG glycosylation pathway using large-scale mass-spectrometry measurements. Gaussian graphical models are used to construct association networks from four cohorts. We find that glycan pairs with high partial correlations represent enzymatic reactions in the known glycosylation pathway, and then predict new biochemical reactions using a rule-based approach. Validation is performed using data from a GWAS and results from three in vitro experiments. We show that one predicted reaction is enzymatically feasible and that one rejected reaction does not occur in vitro. Moreover, in contrast to previous knowledge, enzymes involved in our predictions colocalize in the Golgi of two cell lines, further confirming the in silico predictions.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Genos Glycoscience Research Laboratory HR Croatia (HR) University of Zagreb / Sveučilište u Zagrebu HR Croatia (HR) Oulun Yliopisto / University of Oulo FI Finland (FI) University of Georgia (UGA) US United States (USA) (US) Leiden University NL Netherlands (NL) University of Edinburgh GB United Kingdom (GB) University of Split / Sveučilište u Splitu HR Croatia (HR) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) RU Russian Federation (RU)

How to cite

APA:

Benedetti, E., Pucic-Bakovic, M., Keser, T., Wahl, A., Hassinen, A., Yang, J.-Y.,... Krumsiek, J. (2017). Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway. Nature Communications, 8(1). https://doi.org/10.1038/s41467-017-01525-0

MLA:

Benedetti, Elisa, et al. "Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway." Nature Communications 8.1 (2017).

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