Research - Laboratories of Core Facilities - Laboratory of Bioinformatics

Zoltán HEGEDŰS
senior research associate

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Zoltán GYÖRGYPÁL research associate

The current paradigm of molecular biology is shifting towards the interpretation of data produced by high-throughput methods. The new data sources allow one to study system-wide properties in molecular terms. We are developing novel, generalized knowledge representation schemes for the study of the very complex molecular systems of the living cells like the regulatory network of the gene expression.

GENOME BIOINFORMATICS

The Bioinformatics Group has special expertise in large-scale bioinformatics data management systems that have become an integrating force in systems biology, by providing common platforms and databases for different high-throughput experimental technologies. One of the major focus points of our ongoing research activity is the bioinformatics analysis of experimental data produced by next generation sequencing based transcriptome profiling studies. We are participating in several collaborative projects utilizing RNA-seq or Deep-SAGE techniques for identifying marker genes involved in different pathological conditions. We are also involved in the data processing of targeted resequencing experiments conducted to identify novel disease causing DNA polymorphisms implicated in different inherited heart disorders like hypertrophic cardiomyopathy or long QT syndrome and in the most common, genetically acquired, life-shortening chronic illness cystic fibrosis.


PROTEIN FAMILY ANNOTATION

The identification of the Tribbles family members’ role as regulators of signal processing systems and physiological processes, including development, together with their potential involvement in diabetes and cancer has generated considerable interest in these proteins. Tribbles have been reported to regulate the activation of numerous intracellular signaling pathways, with roles extending from mitosis and cell activation to apoptosis and modulation of gene expression. Within the framework of an international collaboration with the Cardiovascular Research Unit of the University of Sheffield (UK) we are involved in the bioinformatics investigation of the Tribbles family genes and proteins. In addition to the classical bioinformatics techniques we are also applying modern data mining approaches using the publicly available repositories of high throughput transcriptomics experiments (GEO, Array express).


BIOINFORMATICS INFRASTRUCTURE RESOURCES

Most biologists today need some kind of assistance in accessing and analyzing the data available through the Internet and in keeping up with the new bioinformatics analysis methods. Our group played key role in establishing the biocomputing infrastructure of the institute. We have developed BRC BioNet, an HTTP-based intranet resource, which is accessible from any of the over four hundred PCs and workstations in the laboratories. BRC BioNet's tools include:

EMBOSS bioinformatics software suit (~100 programs)
PISE graphical interface for EMBOSS package
Library information and online access to scientific journals
Medline alerting service
Citation database
A repository of local teaching materials
Scientific Toolbox (periodic table, fact sheets about isotopes, vectors, restriction sites, etc.)
A collection of more than a thousand WWW links of biological interest

We also provide institute-wide access to various molecular modeling tools including the SYBYL program package of Tripos Inc. covering the scientific discipline of molecular mechanics, molecular dynamic simulations, homology modeling, ligand docking and threading.

Selected publications

Salazar M, Lorente M, Garcia-Taboada E, Perez Gomez E, Davila D, Zuniga-Garcia P, Maria Flores J, Rodriguez A, Hegedus Z, Mosen-Ansorena D, Aransay A M, Hernandez-Tiedra S, Lopez-Valero I, Quintanilla M, Sanchez C, Iovanna J L, Dusetti N, Guzman M, Francis S E, Carracedo A, Kiss-Toth E, Velasco G The TRIB3 supresses tumorigenesis by controling the mTORC2/AKT/FOXO signaling. Molecular & Cellular Oncology (2014) Accepted for publication

Salazar M, Lorente M, Garcia-Taboada E, Perez Gomez E, Davila D, Zuniga-Garcia P, Maria Flores J, Rodriguez A, Hegedus Z, Mosen-Ansorena D, Aransay A M, Hernandez-Tiedra S, Lopez-Valero I, Quintanilla M, Sanchez C, Iovanna J L, Dusetti N, Guzman M, Francis S E, Carracedo A, Kiss-Toth E, Velasco G Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation. Cell Death Differ. (2014) doi: 10.1038/cdd.2014.133

Attila Farkas, Gergely Maróti, Hajnalka Dürgo, Zoltán Györgypál, Rui M. Lima, Katalin F. Medzihradszky, Attila Kereszt, Peter Mergaert, and Éva Kondorosi Medicago truncatula symbiotic peptide NCR247 contributes to bacteroid differentiation through multiple mechanisms (2014) Proc Natl. Acad. Sci. 111(14) 5183-5188

Filkor K, Hegedűs Z, Szász A, Tubak V, Kemény L, Kondorosi E, Nagy I (2013) Genome Wide Transcriptome Analysis of Dendritic Cells Identifies Genes with Altered Expression in Psoriasis, PLoS ONE 8(9): e73435. doi:10.1371/journal.pone.0073435

Kiss B, Szlanka T, Zvara A, Žurovec M, Sery M, Kakaš S, Ramasz B, Hegedűs Z, Lukacsovich T, Puskás L, Fónagy A, Kiss I (2013) Selective elimination/RNAi silencing of FMRF-related peptides and their receptors decreases the locomotor activity in Drosophila melanogaster, General and Comparative Endocrinology, Vol 191, 137–145

Ordas A, Hegedus Z, Henkel CV, Stockhammer OW, Butler D, Jansen HJ, Racz P, Mink M, Spaink HP, Meijer AH (2010) Deep sequencing of the innate immune transcriptomic response of zebrafish embryos to Salmonella infection Fish & Shellfish Immunology, doi:10.1016/j.fsi.2010.08.022

Hegedus Z, Zakrzewska A, Agoston VC, Ordas A, Racz P, Mink M, Spaink HP, Meijer AH (2009) Deep sequencing of the zebrafish transcriptome response to mycobacterium infection Molecular Immunology, Vol. 46, 2918–2930

Stockhammer, O., Zakrewska, A., Hegedus, Z., Spaink, H. and Meijer A. (2009). Time resolved transcriptome profiling and functional analyses of the zebrafish embryonic host response to Salmonella infection. The Journal of Immunology, 182(9): 5641-5653.

Hegedus, Z., Czibula, A. and Kiss-Toth, E. (2007). Tribbles: a family of kinase-like proteins with potent signalling regulatory function. Cellular Signalling 19(2): 238-250.

Hegedus, Z., Czibula, A. and Kiss-Toth, E. (2006). Tribbles: novel regulators of cell function; evolutionary aspects Cell. Mol.Life Sci. 63(14): 1632-1641.

Vlahovicek, K., Kajan, L., Murvai, J., Hegedus, Z. and Pongor, S. (2003). The SBASE domain sequence library, release 10: domain architecture prediction. Nucleic Acids Research 31(1): 403-405.

Kurucz, E., Zettervall, C.J., Sinka, R., Vilmos, P., Pivarcsi, A., Ekengren, S., Hegedus, Z., Ando, I. and Hultmark, D. (2003). Hemese, a hemocyte-specific transmembrane protein, affects the cellular immune response in Drosophila. Proc. Natl. Acad. Sci. 100(5): 2622-2627.