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Plate IV.409 · Publications

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

Article in Nature Communications, 14 November 2017.

Open accessMetabolite, Association, Metabolomics Data

  1. Elisa Benedetti
  2. Maja Pučić-Baković
  3. Toma Keser
  4. Annika Wahl
  5. Antti Hassinen
  6. Jeong-Yeh Yang
  7. Lin Liu
  8. Irena Trbojević-Akmačić
  9. Genadij Razdorov
  10. Jerko Štambuk
  11. Lucija Klarić
  12. Ivo Ugrina
  13. Maurice H. J. Selman
  14. Manfred Wuhrer
  15. Igor Rudan
  16. Ozren Polasek
  17. Caroline Hayward
  18. Harald Grallert
  19. Konstantin Strauch
  20. Annette Peters
  21. Thomas Meitinger
  22. Christian Gieger
  23. Marija Vilaj
  24. Geert-Jan Boons
  25. Kelley W. Moremen
  26. Tatiana Ovchinnikova
  27. Nicolai Bovin
  28. Sakari Kellokumpu
  29. Fabian J. Theis
  30. Gordan Lauc
  31. Jan Krumsiek

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.

Versions2

  1. CorrectionNature Communications10.1038/s41467-017-02379-2
  2. PublishedNature Communications10.1038/s41467-017-01525-0

Cite

@article{benedetti2017network,
  title = {{Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway}},
  author = {Benedetti, Elisa and Pučić-Baković, Maja and Keser, Toma and Wahl, Annika and Hassinen, Antti and Yang, Jeong-Yeh and Liu, Lin and Trbojević-Akmačić, Irena and Razdorov, Genadij and Štambuk, Jerko and Klarić, Lucija and Ugrina, Ivo and Selman, Maurice H. J. and Wuhrer, Manfred and Rudan, Igor and Polasek, Ozren and Hayward, Caroline and Grallert, Harald and Strauch, Konstantin and Peters, Annette and Meitinger, Thomas and Gieger, Christian and Vilaj, Marija and Boons, Geert-Jan and Moremen, Kelley W. and Ovchinnikova, Tatiana and Bovin, Nicolai and Kellokumpu, Sakari and Theis, Fabian J. and Lauc, Gordan and Krumsiek, Jan},
  journal = {Nature Communications},
  publisher = {Springer Science and Business Media LLC},
  year = {2017},
  month = nov,
  doi = {10.1038/s41467-017-01525-0},
  url = {https://doi.org/10.1038/s41467-017-01525-0},
  pmid = {29133956},
  pmcid = {PMC5684356}
}
.bib file