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

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...

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Autores principales: Benedetti, Elisa, Pučić-Baković, Maja, Keser, Toma, Wahl, Annika, Hassinen, Antti, Yang, Jeong-Yeh, Liu, Lin, Trbojević-Akmačić, Irena, Razdorov, Genadij, Štambuk, Jerko, Klarić, Lucija, Ugrina, Ivo, Selman, Maurice H. J., Wuhrer, Manfred, Rudan, Igor, Polasek, Ozren, Hayward, Caroline, Grallert, Harald, Strauch, Konstantin, Peters, Annette, Meitinger, Thomas, Gieger, Christian, Vilaj, Marija, Boons, Geert-Jan, Moremen, Kelley W., Ovchinnikova, Tatiana, Bovin, Nicolai, Kellokumpu, Sakari, Theis, Fabian J., Lauc, Gordan, Krumsiek, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684356/
https://www.ncbi.nlm.nih.gov/pubmed/29133956
http://dx.doi.org/10.1038/s41467-017-01525-0
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author Benedetti, Elisa
Pučić-Baković, Maja
Keser, Toma
Wahl, Annika
Hassinen, Antti
Yang, Jeong-Yeh
Liu, Lin
Trbojević-Akmačić, Irena
Razdorov, Genadij
Štambuk, Jerko
Klarić, Lucija
Ugrina, Ivo
Selman, Maurice H. J.
Wuhrer, Manfred
Rudan, Igor
Polasek, Ozren
Hayward, Caroline
Grallert, Harald
Strauch, Konstantin
Peters, Annette
Meitinger, Thomas
Gieger, Christian
Vilaj, Marija
Boons, Geert-Jan
Moremen, Kelley W.
Ovchinnikova, Tatiana
Bovin, Nicolai
Kellokumpu, Sakari
Theis, Fabian J.
Lauc, Gordan
Krumsiek, Jan
author_facet Benedetti, Elisa
Pučić-Baković, Maja
Keser, Toma
Wahl, Annika
Hassinen, Antti
Yang, Jeong-Yeh
Liu, Lin
Trbojević-Akmačić, Irena
Razdorov, Genadij
Štambuk, Jerko
Klarić, Lucija
Ugrina, Ivo
Selman, Maurice H. J.
Wuhrer, Manfred
Rudan, Igor
Polasek, Ozren
Hayward, Caroline
Grallert, Harald
Strauch, Konstantin
Peters, Annette
Meitinger, Thomas
Gieger, Christian
Vilaj, Marija
Boons, Geert-Jan
Moremen, Kelley W.
Ovchinnikova, Tatiana
Bovin, Nicolai
Kellokumpu, Sakari
Theis, Fabian J.
Lauc, Gordan
Krumsiek, Jan
author_sort Benedetti, Elisa
collection PubMed
description 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.
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spelling pubmed-56843562017-11-17 Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway Benedetti, Elisa Pučić-Baković, Maja Keser, Toma Wahl, Annika Hassinen, Antti Yang, Jeong-Yeh Liu, Lin Trbojević-Akmačić, Irena Razdorov, Genadij Štambuk, Jerko Klarić, Lucija Ugrina, Ivo Selman, Maurice H. J. Wuhrer, Manfred Rudan, Igor Polasek, Ozren Hayward, Caroline Grallert, Harald Strauch, Konstantin Peters, Annette Meitinger, Thomas Gieger, Christian Vilaj, Marija Boons, Geert-Jan Moremen, Kelley W. Ovchinnikova, Tatiana Bovin, Nicolai Kellokumpu, Sakari Theis, Fabian J. Lauc, Gordan Krumsiek, Jan Nat Commun Article 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. Nature Publishing Group UK 2017-11-14 /pmc/articles/PMC5684356/ /pubmed/29133956 http://dx.doi.org/10.1038/s41467-017-01525-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Benedetti, Elisa
Pučić-Baković, Maja
Keser, Toma
Wahl, Annika
Hassinen, Antti
Yang, Jeong-Yeh
Liu, Lin
Trbojević-Akmačić, Irena
Razdorov, Genadij
Štambuk, Jerko
Klarić, Lucija
Ugrina, Ivo
Selman, Maurice H. J.
Wuhrer, Manfred
Rudan, Igor
Polasek, Ozren
Hayward, Caroline
Grallert, Harald
Strauch, Konstantin
Peters, Annette
Meitinger, Thomas
Gieger, Christian
Vilaj, Marija
Boons, Geert-Jan
Moremen, Kelley W.
Ovchinnikova, Tatiana
Bovin, Nicolai
Kellokumpu, Sakari
Theis, Fabian J.
Lauc, Gordan
Krumsiek, Jan
Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
title Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
title_full Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
title_fullStr Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
title_full_unstemmed Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
title_short Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
title_sort network inference from glycoproteomics data reveals new reactions in the igg glycosylation pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684356/
https://www.ncbi.nlm.nih.gov/pubmed/29133956
http://dx.doi.org/10.1038/s41467-017-01525-0
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