Genome-Wide Association Study on Immunoglobulin G Glycosylation Patterns

Abstract: Technological advances in mass spectrometry imaging (MSI) have contributed to growing interest in 3D MSI. However, the large size of 3D MSI data sets has made their efficient analysis and visualization and the identification of informative molecular patterns computationally challenging. Hierarchical stochastic neighbor embedding (HSNE), a nonlinear dimensionality reduction technique that aims at finding hierarchical and multiscale representations of large data sets, is a recent development that enables the analysis of millions of data points, with manageable time and memory complexities. We demonstrate that HSNE can be used to analyze large 3D MSI data sets at full mass spectral and spatial resolution. To benchmark the technique as well as demonstrate its broad applicability, we have analyzed a number of publicly available 3D MSI data sets, recorded from various biological systems and spanning different mass-spectrometry ionization techniques. We demonstrate that HSNE is able to rapidly identify regions of interest within these large high-dimensionality data sets as well as aid the identification of molecular ions that characterize these regions of interest; furthermore, through clearly separating measurement artifacts, the HSNE analysis exhibits a degree of robustness to measurement batch effects, spatially correlated noise, and mass spectral misalignment.

Annika Wahl, Erik van den Akker, Lucija Klaric, Jerko Stambuk, Elisa Benedetti, et al. Genome-Wide Association Study on Immunoglobulin G Glycosylation Patterns. Frontiers in Immunology, 2018.
@article { bib:2018_front_immunol_igggwas
author = { Annika Wahl and Erik van den Akker and Lucija Klaric and Jerko Stambuk and Elisa Benedetti and Rosina Plomp and Genadij Razdorov and Irena Trbojevic-Akmacic and Joris Deelen and Diana van Heemst and P. Eline Slagboom and Frano Vuckovic and Harald Grallert and Jan Krumsiek and Konstantin Strauch and Annette Peters and Thomas Meitinger and Caroline Hayward and Manfred Wuhrer and Marian Beekman and Gordan Lauc and Christian Gieger },
title = { Genome-Wide Association Study on Immunoglobulin G Glycosylation Patterns },
journal = { Frontiers in Immunology },
year = { 2018 },
doi = { 10.3389/fimmu.2018.00277 },
IgG_GWAS screenshot