ORCID Profile
0000-0002-1287-0906
Current Organisation
Karolinska Institutet
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Publisher: Wiley
Date: 04-2014
Abstract: Scanning MS by MALDI MS imaging (MALDI-MSI) creates large volumetric global datasets that describe the location and identity of ions registered at each s ling location. While thousands of ion peaks are recorded in a typical whole-tissue analysis, only a fraction of these measured molecules are purposefully scrutinized within a given experimental design. To address this need, we recently reported new methods to query the full volume of MALDI-MSI data that correlate all ion masses to one another. As an ex le of this utility, we demonstrate that specific ion peak m/z signatures can be used to localize similar histological structures within tissue s les. In this study, we use the ex le of ion peak masses that are associated with tissue spaces occupied by airway bronchioles in rat lung s les. The volume of raw data was preprocessed into structures of 0.1 mass unit bins containing metadata collected at each s ling position. Interactive visualization in ParaView identified ion peaks that especially showed strong association with airway bronchioles but not vascular or parenchymal tissue compartments. Further iterative statistical correlation queries provided ranked indices of all m/z values in the global dataset regarding coincident distributions at any given X, Y position in the histological spaces occupied by bronchioles The study further provides methods for extracting important information contained in global datasets that previously was unseen or inaccessible.
Publisher: Cold Spring Harbor Laboratory
Date: 26-03-2022
DOI: 10.1101/2022.03.26.485908
Abstract: Excessive production of reactive oxygen species (ROS) is characteristic of numerous diseases, but most studies in this area have not considered the impact of endogenous antioxidative defenses. Here, utilizing multi-omics, we demonstrate that in cardiomyocytes mitochondrial isocitrate dehydrogenase (IDH2) constitutes a major antioxidant defense. In both male and female mice and humans the paradoxical reduction in expression of IDH2 associated with heart failure is compensated for by an increase in the enzyme’s activity. We describe extensive mutual regulation of the antioxidant activities of IDH2 and NRF2 by a network involving 2-oxoglutarate and L2-hydroxyglutarate and mediated in part through unconventional hydroxymethylation of cytosine residues present in introns. Conditional targeting of ROS in a murine model of heart failure improves cardiac function. Together, these insights may explain why previous attempts to treat heart failure with antioxidants have been unsuccessful and open new approaches to personalizing and, thereby, improving such treatment. Paradoxical downregulation of mitochondrial isocitrate dehydrogenase (IDH2) in response to oxidative stress leads to the discovery of a robust antioxidative defense in the heart. An antioxidative loop involving IDH2 coordinates other antioxidative defenses, such as NRF2. This loop produces epigenetic modifications that link oxidative stress to mitochondrial function. The conclusion that enhancing antioxidative capacity improves cardiac function only when the endogenous capacity is insufficient opens new approaches to in idualized treatment of patients with heart failure.
Publisher: American Chemical Society (ACS)
Date: 23-07-2015
DOI: 10.1021/PR5013009
Abstract: This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological s les that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wiki (c-hpp.webhosting.rug.nl/) and in the Supporting Information.
Publisher: American Chemical Society (ACS)
Date: 16-04-2013
DOI: 10.1021/AC303658T
Abstract: Mass spectrometry imaging (MSI) generates large volumetric data sets consisting of mass to charge ratio (m/z), ion current, and x,y coordinate location. These data sets usually serve limited purposes centered on measuring the distribution of a small set of ions with known m/z. Such earmarked queries consider only a fraction of the full mass spectrum captured, and there are few tools to assist the exploration of the remaining volume of unknown data in terms of demonstrating similarity or discordance in tissue compartment distribution patterns. Here we present a novel, interactive approach to extract information from MSI data that relies on precalculated data structures to perform queries of large data sets with a typical laptop. We have devised methods to query the full volume to find new m/z values of potential interest based on similarity to biological structures or to the spatial distribution of known ions. We describe these query methods in detail and provide ex les demonstrating the power of the methods to "discover" m/z values of ions that have such potentially interesting correlations. The "discovered" ions may be further correlated with either positional locations or the coincident distribution of other ions using successive queries. Finally, we show it is possible to gain insight to the fragmentation pattern of the parent molecule from such correlations. The ability to discover new ions of interest in the unknown bulk of an MSI data set offers the potential to further our understanding of biological and physiological processes related to health and disease.
Location: United States of America
No related grants have been discovered for Akos Vegvari.