TY - GEN AU - Turek, Cezary AU - Olbei, Marton AU - Stirling, Tamás AU - Fekete, Gergely AU - Tasnádi, Ervin Áron AU - Gul, Leila AU - Bohár, Balázs AU - Papp, Balázs AU - Jurkowski, Wiktor AU - Ari, Eszter TI - mulea - an R package for enrichment analysis using multiple ontologies and empirical FDR correction PY - 2024 UR - https://m2.mtmt.hu/api/publication/34718081 ID - 34718081 AB - Traditional gene set enrichment analyses are typically limited to a few ontologies and do not account for the interdependence of gene sets or terms, resulting in overcorrected p-values. To address these challenges, we introduce mulea, an R package offering comprehensive overrepresentation and functional enrichment analysis. mulea employs an innovative empirical false discovery rate (eFDR) correction method, specifically designed for interconnected biological data, to accurately identify significant terms within diverse ontologies. mulea expands beyond traditional tools by incorporating a wide range of ontologies, encompassing Gene Ontology, pathways, regulatory elements, genomic locations, and protein domains. This flexibility enables researchers to tailor enrichment analysis to their specific questions, such as identifying enriched transcriptional regulators in gene expression data or overrepresented protein domains in protein sets. To facilitate seamless analysis, mulea provides gene sets (in standardised GMT format) for 27 model organisms, covering 16 databases and various identifiers resulting in almost 900 files. Additionally, the muleaData ExperimentData Bioconductor package simplifies access to these pre-defined ontologies. Finally, mulea's architecture allows for easy integration of user-defined ontologies, expanding its applicability across diverse research areas. Availability and Implementation: Software for the tools demonstrated in this article is available as an R package on GitHub: https://github.com/ELTEbioinformatics/mulea. LA - English DB - MTMT ER - TY - JOUR AU - Tengölics, Roland AU - Szappanos, Balázs AU - Mülleder, M AU - Kalapis, Dorottya AU - Grézal, Gábor AU - Sajben, Cs AU - Agostini, F AU - Mokochinski, Joao Benhur AU - Bálint, Balázs AU - Nagy, LG AU - Ralser, M AU - Papp, Balázs TI - The metabolic domestication syndrome of budding yeast JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 121 PY - 2024 IS - 11 PG - 11 SN - 0027-8424 DO - 10.1073/pnas.2313354121 UR - https://m2.mtmt.hu/api/publication/34479463 ID - 34479463 LA - English DB - MTMT ER - TY - JOUR AU - Liska, Orsolya AU - Boross, Gábor AU - Rocabert, Charles AU - Szappanos, Balázs AU - Tengölics, Roland AU - Papp, Balázs TI - Principles of metabolome conservation in animals JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 120 PY - 2023 IS - 35 PG - 12 SN - 0027-8424 DO - 10.1073/pnas.2302147120 UR - https://m2.mtmt.hu/api/publication/34202172 ID - 34202172 N1 - Funding Agency and Grant Number: "Lendlet" program of the Hungarian Academy of Sciences [LP2009-013/2012]; European Union [739593]; National Laboratory for Health Security [RRF-2.3.1-21-2022-00006]; National Laboratory of Biotechnology [NKFIH-871-3]; Hungarian Academy of Sciences Premium Postdoctoral Research Program [PREMIUM-2018-294]; Hungarian Academy of Sciences [BO/00728/21/8]; New National Excellence Program of the Ministry of Human Capacities [UNKP-21-5-SZTE-564, UNKP-22-5-SZTE-592]; National Research, Development and Innovation Office [PD 128271]; Tobacco-Related Disease Research Program of the University of California [T31FT1772] Funding text: by the National Research, Development and Innovation Office Elvonal Program KKP 129814 (B.P.) , the "Lenduelet" program of the Hungarian Academy of Sciences LP2009-013/2012 (B.P.) ,the European Union's Horizon 2020 research and innovation program Grant No. 739593 (B.P.) , the National Laboratory for Health Security Grant RRF-2.3.1-21-2022-00006 (B.P.) , the National Laboratory of Biotechnology Grant NKFIH-871-3/2020 (B.P.) , The Hungarian Academy of Sciences Premium Postdoctoral Research Program (PREMIUM-2018-294 to B.S.) ,Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences (BO/00728/21/8 to B.S.) , New National Excellence Program of the Ministry of Human Capacities (Bolyai+, UNKP-21-5-SZTE-564 and UNKP-22-5-SZTE-592 to B.S.) , National Research, Development and Innovation Office (PD 128271 to R.T.) and the Tobacco-Related Disease Research Program of the University of California (T31FT1772 to G.B.) . AB - Metabolite levels shape cellular physiology and disease susceptibility, yet the general principles governing metabolome evolution are largely unknown. Here, we introduce a measure of conservation of individual metabolite levels among related species. By analyzing multispecies tissue metabolome datasets in phylogenetically diverse mammals and fruit flies, we show that conservation varies extensively across metabolites. Three major functional properties, metabolite abundance, essentiality, and association with human diseases predict conservation, highlighting a striking parallel between the evolutionary forces driving metabolome and protein sequence conservation. Metabolic network simulations recapitulated these general patterns and revealed that abundant metabolites are highly conserved due to their strong coupling to key metabolic fluxes in the network. Finally, we show that biomarkers of metabolic diseases can be distinguished from other metabolites simply based on evolutionary conservation, without requiring any prior clinical knowledge. Overall, this study uncovers simple rules that govern metabolic evolution in animals and implies that most tissue metabolome differences between species are permitted, rather than favored by natural selection. More broadly, our work paves the way toward using evolutionary information to identify biomarkers, as well as to detect pathogenic metabolome alterations in individual patients. LA - English DB - MTMT ER - TY - JOUR AU - Pál, Csaba AU - Papp, Balázs TI - How selection shapes the short- and long-term dynamics of molecular evolution JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 120 PY - 2023 IS - 33 PG - 3 SN - 0027-8424 DO - 10.1073/pnas.2311012120 UR - https://m2.mtmt.hu/api/publication/34106372 ID - 34106372 N1 - Synthetic and System Biology Unit, Biological Research Centre, National Laboratory of Biotechnology, Eötvös Loránd Research Network, Szeged, HU-6726, Hungary Hungarian Centre of Excellence for Molecular Medicine, Biological Research Centre Metabolic Systems Biology Research Group, Szeged, HU-6726, Hungary National Laboratory for Health Security, Biological Research Centre, Eötvös Loránd Research Network, Szeged, HU-6726, Hungary Export Date: 22 January 2024 CODEN: PNASA Correspondence Address: Pála, C.; Synthetic and System Biology Unit, Hungary; email: cpal@brc.hu LA - English DB - MTMT ER - TY - JOUR AU - Szatmári, Orsolya AU - Nagy-Mikó, Bence AU - Györkei, Ádám AU - Varga, Dániel AU - H. Kovács, Bálint Barna AU - Igaz, Nóra AU - Bognár, Bence AU - Rázga, Zsolt AU - Nagy, Gábor AU - Zsindely, Nóra AU - Bodai, László AU - Papp, Balázs AU - Erdélyi, Miklós AU - Csontné Kiricsi, Mónika AU - Blastyák, András AU - Collart, Martine A AU - Boros, Imre Miklós AU - Villanyi, Zoltan TI - Phase-separated ribosome-nascent chain complexes in genotoxic stress response JF - RNA-A PUBLICATION OF THE RNA SOCIETY J2 - RNA VL - 29 PY - 2023 IS - 10 SP - 1557 EP - 1574 PG - 18 SN - 1355-8382 DO - 10.1261/rna.079755.123 UR - https://m2.mtmt.hu/api/publication/34067381 ID - 34067381 N1 - Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, 6726, Hungary Institute of Biochemistry, Biological Research Centre, Szeged, 6726, Hungary Section for Physiology and Cell Biology, Department of Biosciences, University of Oslo, Oslo, 0316, Norway Department of Optics and Quantum Electronics, University of Szeged, Szeged, 6720, Hungary Department of Pathology, Faculty of Medicine, University of Szeged, Szeged, 6720, Hungary Institute of Genetics, Biological Research Centre, Szeged, 6726, Hungary Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva 4, 1211, Switzerland Cited By :1 Export Date: 12 December 2023 CODEN: RNARF Correspondence Address: Villányi, Z.; Department of Biochemistry and Molecular Biology, Hungary; email: villanyi.zoltan@bio.u-szeged.hu Chemicals/CAS: 1,6 hexanediol, 629-11-8; DNA helicase; edetic acid, 150-43-6, 60-00-4; ribonuclease, 59794-03-5, 9001-99-4; transcriptional regulator ATRX; Werner syndrome ATP dependent helicase; RNA, 63231-63-0; Edetic Acid; RecQ Helicases; Ribonucleoproteins; RNA; Saccharomyces cerevisiae Proteins; SGS1 protein, S cerevisiae Funding details: 31003A_172999, NTP-NFTÖ-20-B-0354 Funding details: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF Funding details: Magyar Tudományos Akadémia, MTA, BO/00878/19/8, BO/902/19, TKP2021-NVA-19 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI Funding text 1: We are grateful to Dr. Balázs Vedelek and Dr. Zsuzsa Sarkadi for valuable discussions. We thank Jawad Iqbal, Elvira Czvik, Zita Kóra, and Edina Pataki for technical assistance. We are grateful to Blanka Léhy for the graphical abstract. This work was supported by grants GINOP-2.3.2-15-2016-00020 and GINOP-2.3.2-15-2016-00038, as well as by NKFI-K 142961 (Z.V.), ÚNKP-21-5-595-SZTE (Z.V.), and ÚNKP-20-5-SZTE-655 (M.K.) from the Hungarian National Research, Development and Innovation Office. Further support was provided by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/902/19 for Z.V. and BO/00878/19/8 for M.K.). Superresolu-tion dSTORM experiments and their evaluation were funded by the Hungarian National Research, Development and Innovation Office (TKP2021-NVA-19), Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002) awarded to M.E., and NTP-NFTÖ-20-B-0354 awarded to D.V., as well as grant 31003A_172999 from the Swiss National Science Foundation awarded to M.A.C. AB - Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered N-terminal part of the nascent chain was found to be indispensable for the accumulation of the Rpt1-RNP into assemblysomes. Motivated by this, to find other assemblysome-associated RNPs we used bioinformatics to rank subunits of Saccharomyces cerevisiae protein complexes according to their N-terminal disorder propensity. The results revealed that gene products involved in DNA repair are enriched among the top candidates. The Sgs1 DNA helicase was chosen for experimental validation. We found that indeed nascent chains of Sgs1 form EDTA-resistant RNP condensates, assemblysomes by definition. Moreover, upon exposure to UV, SGS1 mRNA shifted from assemblysomes to polysomes, suggesting that external stimuli are regulators of assemblysome dynamics. We extended our studies to human cell lines. The BLM helicase, ortholog of yeast Sgs1, was identified upon sequencing assemblysome-associated RNAs from the MCF7 human breast cancer cell line, and mRNAs encoding DNA repair proteins were overall enriched. Using the radiation-resistant A549 cell line, we observed by transmission electron microscopy that 1,6-hexanediol, an agent known to disrupt phase-separated condensates, depletes ring ribosome structures compatible with assemblysomes from the cytoplasm of cells and makes the cells more sensitive to X-ray treatment. Taken together these findings suggest that assemblysomes may be a component of the DNA damage response from yeast to human. LA - English DB - MTMT ER - TY - JOUR AU - Apjok, Gábor AU - Számel, Mónika AU - Christodoulou, Chryso AU - Seregi, Viktória AU - Vásárhelyi, Bálint Márk AU - Stirling, Tamás AU - Eszenyi, Bálint Dénes AU - Sári , Tóbiás AU - Vidovics, Fanni AU - Nagrand, Erika AU - Kovács, Dorina AU - Szili, Petra AU - Lantos, Ildikó Ilona AU - Méhi, Orsolya Katinka AU - Jangir, Pramod Kumar AU - Herczeg, Róbert AU - Gálik, Bence AU - Urbán, Péter AU - Gyenesei, Attila AU - Draskovits, Gábor AU - Nyerges, Ákos AU - Fekete, Gergely AU - Bodai, László AU - Zsindely, Nóra AU - Dénes, Béla AU - Yosef, Ido AU - Qimron, Udi AU - Papp, Balázs AU - Pál, Csaba AU - Kintses, Bálint TI - Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains JF - NATURE MICROBIOLOGY J2 - NAT MICROBIOL VL - 8 PY - 2023 IS - 3 SP - 410 EP - 423 PG - 14 SN - 2058-5276 DO - 10.1038/s41564-023-01320-2 UR - https://m2.mtmt.hu/api/publication/33634821 ID - 33634821 N1 - Funding Agency and Grant Number: National Laboratory of Biotechnology Grants [NKFIH-871-3/2020, 2022-2.1.1-NL-2022-00008]; European Union [754432]; European Research Council [648364, 862077]; National Research, Development and Innovation Office grant [FK-135245, FK-124254]; National Research, Development and Innovation Office; Ministry for Innovation and Technology [KKP 129814, 126506]; New National Excellence Program of the Ministry of Human Capacities [UNKP-20-5-SZTE-654, UNKP-21-5-SZTE-579]; New National Excellence Program of the Ministry for Innovation and Technology - National Research, Development and Innovation Fund [UNKP-20-3 -SZTE-452]; Doctoral Student Scholarship Program of the Co-Operative Doctoral Program of the Ministry of Innovation and Technology - National Research, Development and Innovation Fund [KDP-17-4/ PALY-2021, C992025]; European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant [754432]; Polish Ministry of Science and Higher Education; National Academy of Scientist Education Program of the National Biomedical Foundation under Hungarian Ministry of Culture and Innovation; National Laboratory for Health Security [RRF-2.3.1-212022-00006, GINOP-2.3.2-15-2016-00014, GINOP-2.3.2-15-2016-00020, GINOP-2.3.2-15-2016-00035]; Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences [BO/352/20, BO/00303/19/8]; [GINOP-2.3.4-15-2020-00010]; [GINOP-2.3.1-20-2020-00001]; [BECOMING-2019-1-HU01-KA203-061251] Funding text: We thank D. Verma from the Department of Microbiology and B. Bhimrao of Ambedkar University, Lucknow, India for help with soil sample collection and NBA approval. This work was supported by National Laboratory of Biotechnology Grants NKFIH-871-3/2020 and 2022-2.1.1-NL-2022-00008 (B.K. and C.P.); the European Union's Horizon 2020 research and innovation programme under grant agreement no. 739593 (B.P. and B.K.); the European Research Council H2020-ERC-2014-CoG 648364-Resistance Evolution (C.P.) and H2020-ERC-2019-PoC 862077-Aware (C.P.); National Research, Development and Innovation Office grant FK-135245 (B.K.) and FK-124254 (O.M.); the National Research, Development and Innovation Office and the Ministry for Innovation and Technology under the `Frontline' Programme KKP 129814 and 126506 (B.P. and C.P.); the National Laboratory for Health Security RRF-2.3.1-212022-00006 (B.P.), GINOP-2.3.2-15-2016-00014 (EVOMER, C.P. and B.P.), GINOP-2.3.2-15-2016-00020 (MolMedEx TUMORDNS, C.P.), GINOP-2.3.2-15-2016-00035 (N.Z.); a Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences (BO/352/20 (B.K.), BO/00303/19/8 (O.M)); New National Excellence Program of the Ministry of Human Capacities (UNKP-20-5-SZTE-654 and UNKP-215-SZTE-579, B.K.); New National Excellence Program of the Ministry for Innovation and Technology funded by the National Research, Development and Innovation Fund (UNKP-20-3 -SZTE-452, G.A.); the Doctoral Student Scholarship Program of the Co-Operative Doctoral Program of the Ministry of Innovation and Technology financed by the National Research, Development and Innovation Fund (KDP-17-4/ PALY-2021, C992025, M.S.). R.H., B.G., P.U. and A.G. were supported by GINOP-2.3.4-15-2020-00010, GINOP-2.3.1-20-2020-00001, BECOMING-2019-1-HU01-KA203-061251, the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 754432 and the Polish Ministry of Science and Higher Education, from the financial resources for science in 2018-2023. This research work was conducted with the support of the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (D.K.). AB - Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. Here we present a functional metagenomics pipeline called Reprogrammed Bacteriophage Particle Assisted Multi-species Functional Metagenomics (DEEPMINE). This approach combines and improves the use of T7 bacteriophage with exchanged tail fibres and targeted mutagenesis to expand phage host-specificity and efficiency for functional metagenomics. These modified phage particles were used to introduce large metagenomic plasmid libraries into clinically relevant bacterial pathogens. By screening for ARGs in soil and gut microbiomes and clinical genomes against 13 antibiotics, we demonstrate that this approach substantially expands the list of identified ARGs. Many ARGs have species-specific effects on resistance; they provide a high level of resistance in one bacterial species but yield very limited resistance in a related species. Finally, we identified mobile ARGs against antibiotics that are currently under clinical development or have recently been approved. Overall, DEEPMINE expands the functional metagenomics toolbox for studying microbial communities. LA - English DB - MTMT ER - TY - JOUR AU - Grézal, Gábor AU - Spohn, Réka AU - Méhi, Orsolya Katinka AU - Dunai, Anett AU - Lázár, Viktória AU - Bálint, Balázs AU - Nagy, István AU - Pál, Csaba AU - Papp, Balázs TI - Plasticity and stereotypic rewiring of the transcriptome upon bacterial evolution of antibiotic resistance JF - MOLECULAR BIOLOGY AND EVOLUTION J2 - MOL BIOL EVOL VL - 40 PY - 2023 IS - 2 SN - 0737-4038 DO - 10.1093/molbev/msad020 UR - https://m2.mtmt.hu/api/publication/33632100 ID - 33632100 N1 - Funding Agency and Grant Number: Lendulet program of the Hungarian Academy of Sciences [LP-2009-013/2012, LP-2012-32/2018]; ELKH Lenduelet program [LP-2017-2010/2020]; Wellcome Trust WT [098016/Z/11/Z]; European Research Council [648364, 862077]; National Research, Development and Innovation Office; Ministry for Innovation and Technology [KKP KH125616, 126506, RRF-2.3.1-21-2022-00006, GINOP-2.3.2-15-2016-00026, GINOP-2.3.2-15-2 016-00014, GINOP-2.3.2-15-2 016-00020]; National Laboratory of Biotechnology Grant [2022-2.1.1-NL-2022-00008]; European Union [739593]; NKFIH [FK124254]; Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences [BO/608/21] Funding text: This work was supported by the "Lendulet" program of the Hungarian Academy of Sciences LP-2009-013/2012 (B.P.), LP-2012-32/2018 (C.P.), the ELKH Lenduelet program LP-2017-2010/2020 (C.P.), the Wellcome Trust WT 098016/Z/11/Z (B.P.), The European Research Council H2020-ERC-2014-CoG 648364-Resistance Evolution (C.P.), and H2020-ERC-2019-PoC 862077-Aware (C.P.), the National Research, Development and Innovation Office and the Ministry for Innovation and Technology under the "Frontline" program KKP KH125616 and 126506 (B.P. and C.P.), RRF-2.3.1-21-2022-00006 (B.P.), GINOP-2.3.2-15-2016-00026 (iChamber, B.P.), GINOP-2.3.2-15-2 016-00014 (EVOMER, C.P. and B.P.), GINOP-2.3.2-15-2 016-00020 (MolMedEx TUMORDNS, C.P.), National Laboratory of Biotechnology Grant 2022-2.1.1-NL-2022-00008 (C.P. and B.P.), The European Union's Horizon 202 0 research and innovation program under grant agreement No 739593 (B.P.). NKFIH grant FK124254 (O.M.), the Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences BO/608/21 (R.S.). AB - Bacterial evolution of antibiotic resistance frequently has deleterious side effects on microbial growth, virulence, and susceptibility to other antimicrobial agents. However, it is unclear how these trade-offs could be utilized for manipulating antibiotic resistance in the clinic, not least because the underlying molecular mechanisms are poorly understood. Using laboratory evolution, we demonstrate that clinically relevant resistance mutations in Escherichia coli constitutively rewire a large fraction of the transcriptome in a repeatable and stereotypic manner. Strikingly, lineages adapted to functionally distinct antibiotics and having no resistance mutations in common show a wide range of parallel gene expression changes that alter oxidative stress response, iron homeostasis, and the composition of the bacterial outer membrane and cell surface. These common physiological alterations are associated with changes in cell morphology and enhanced sensitivity to antimicrobial peptides. Finally, the constitutive transcriptomic changes induced by resistance mutations are largely distinct from those induced by antibiotic stresses in the wild-type. This indicates a limited role for genetic assimilation of the induced antibiotic stress response during resistance evolution. Our work suggests that diverse resistance mutations converge on similar global transcriptomic states that shape genetic susceptibility to antimicrobial compounds. LA - English DB - MTMT ER - TY - JOUR AU - Correia-Melo, C. AU - Kamrad, S. AU - Tengölics, Roland AU - Messner, C.B. AU - Trebulle, P. AU - Townsend, S. AU - Jayasree, Varma S. AU - Freiwald, A. AU - Heineike, B.M. AU - Campbell, K. AU - Herrera-Dominguez, L. AU - Kaur, Aulakh S. AU - Szyrwiel, L. AU - Yu, J.S.L. AU - Zelezniak, A. AU - Demichev, V. AU - Mülleder, M. AU - Papp, Balázs AU - Alam, M.T. AU - Ralser, M. TI - Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan JF - CELL J2 - CELL VL - 186 PY - 2023 IS - 1 SP - 63 EP - 79.e21 SN - 0092-8674 DO - 10.1016/j.cell.2022.12.007 UR - https://m2.mtmt.hu/api/publication/33552618 ID - 33552618 N1 - The Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, London, NW1 1AT, United Kingdom Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, United Kingdom Department of Biochemistry, Charité – Universitätsmedizin Berlin, Berlin, 10117, Germany Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, 6726, Hungary HCEMM-BRC Metabolic Systems Biology Lab, Szeged, 6726, Hungary Precision Proteomics Center, Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, 7265, Switzerland The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom Core Facility – High Throughput Mass Spectrometry, Charité – Universitätsmedizin Berlin, Berlin, 10117, Germany Quantitative Gene Expression Research Group, MRC London Institute of Medical Sciences (LMS), London, W12 0HS, United Kingdom Quantitative Gene Expression Research Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, SW2 2AZ, United Kingdom Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, 412 96, Sweden Randall Centre for Cell & Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, United Kingdom Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, 10257, Lithuania Department of Biology, College of Science, United Arab Emirates University, P.O.Box 15551, Al-Ain, United Arab Emirates Export Date: 10 January 2023 CODEN: CELLB Correspondence Address: Correia-Melo, C.; The Molecular Biology of Metabolism Laboratory, United Kingdom; email: claramelo85@gmail.com Correspondence Address: Ralser, M.; The Molecular Biology of Metabolism Laboratory, United Kingdom; email: markus.ralser@charite.de AB - Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained with intracellular metabolism, growth control, and signaling. Studying chronological aging in yeast, we reveal a so far overlooked metabolic property that influences aging via the exchange of metabolites. We observed that metabolites exported by young cells are re-imported by chronologically aging cells, resulting in cross-generational metabolic interactions. Then, we used self-establishing metabolically cooperating communities (SeMeCo) as a tool to increase metabolite exchange and observed significant lifespan extensions. The longevity of the SeMeCo was attributable to metabolic reconfigurations in methionine consumer cells. These obtained a more glycolytic metabolism and increased the export of protective metabolites that in turn extended the lifespan of cells that supplied them with methionine. Our results establish metabolite exchange interactions as a determinant of cellular aging and show that metabolically cooperating cells can shape the metabolic environment to extend their lifespan. © 2022 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Liska, Orsolya AU - Bohár, Balázs AU - Hidas, András AU - Korcsmáros, Tamás AU - Papp, Balázs AU - Fazekas, Dávid AU - Ari, Eszter TI - TFLink: an integrated gateway to access transcription factor–target gene interactions for multiple species JF - DATABASE-JOURNAL OF BIOLOGICAL DATABASES AND CURATION J2 - DATABASE-OXFORD VL - 2022 PY - 2022 SN - 1758-0463 DO - 10.1093/database/baac083 UR - https://m2.mtmt.hu/api/publication/33101945 ID - 33101945 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office, Hungary (NKFIH) [131839]; NKFIH KKP [129814]; GINOP iChamber [2.3.215-2016-00026]; European Union [739593]; Biotechnology and Biological Sciences Research Council (BBSRC) Core Strategic Programme Grant [BB/CSP17270/1]; BBSRC ISP grant [BB/R012490/1] Funding text: This work was supported by the National Research, Development and Innovation Office, Hungary (NKFIH) grant PD [grant number 131839 to E.A.]; an NKFIH KKP [grant number 129814 to B.P.]; GINOP iChamber [grant number 2.3.215-2016-00026 to B.P.]; and The European Union's Horizon 2020 research and innovation programme under grant agreement [grant number 739593 to B.P.]; a Biotechnology and Biological Sciences Research Council (BBSRC) Core Strategic Programme Grant [grant number BB/CSP17270/1 to T.K.]; and a BBSRC ISP grant [grant number BB/R012490/1 to T.K.]. AB - Analysis of transcriptional regulatory interactions and their comparisons across multiple species are crucial for progress in various fields in biology, from functional genomics to the evolution of signal transduction pathways. However, despite the rapidly growing body of data on regulatory interactions in several eukaryotes, no databases exist to provide curated high-quality information on transcription factor–target gene interactions for multiple species. Here, we address this gap by introducing the TFLink gateway, which uniquely provides experimentally explored and highly accurate information on transcription factor–target gene interactions (∼12 million), nucleotide sequences and genomic locations of transcription factor binding sites (∼9 million) for human and six model organisms: mouse, rat, zebrafish, fruit fly, worm and yeast by integrating 10 resources. TFLink provides user-friendly access to data on transcription factor–target gene interactions, interactive network visualizations and transcription factor binding sites, with cross-links to several other databases. Besides containing accurate information on transcription factors, with a clear labelling of the type/volume of the experiments (small-scale or high-throughput), the source database and the original publications, TFLink also provides a wealth of standardized regulatory data available for download in multiple formats. The database offers easy access to high-quality data for wet-lab researchers, supplies data for gene set enrichment analyses and facilitates systems biology and comparative gene regulation studies. LA - English DB - MTMT ER - TY - JOUR AU - Ari, Eszter AU - Vásárhelyi, Bálint Márk AU - Kemenesi, Gábor AU - Tóth, Gábor Endre AU - Zana, Brigitta AU - Somogyi, Balázs Antal AU - Lanszki, Zsófia AU - Röst, Gergely AU - Jakab, Ferenc AU - Papp, Balázs AU - Kintses, Bálint TI - A Single Early Introduction Governed Viral Diversity in the Second Wave of SARS-CoV-2 Epidemic in Hungary JF - VIRUS EVOLUTION J2 - VIRUS EVOL VL - 8 PY - 2022 IS - 2 PG - 12 SN - 2057-1577 DO - 10.1093/ve/veac069 UR - https://m2.mtmt.hu/api/publication/33040340 ID - 33040340 AB - Retrospective evaluation of past waves of the SARS-CoV-2 epidemic is key for designing optimal interventions against future waves and novel pandemics. Here we report on analysing genome sequences of SARS-CoV-2 from the first two waves of the epidemic in 2020 in Hungary, mirroring a suppression and a mitigation strategy, respectively. Our analysis reveals that the two waves markedly differed in viral diversity and transmission patterns. Specifically, unlike in several European areas or in the USA, we have found no evidence for early introduction and cryptic transmission of the virus in the first wave of the pandemic in Hungary. Despite the introduction of multiple viral lineages, extensive community spread was prevented by a timely national lockdown in March 2020. In sharp contrast, the majority of the cases in the much larger second wave can be linked to a single transmission lineage of the pan-European B.1.160 variant. This lineage was introduced unexpectedly early, followed by a two-month-long cryptic transmission before a soar of detected cases in September 2020. Epidemic analysis has revealed that the dominance of this lineage in the second wave was not associated with an intrinsic transmission advantage. This finding is further supported by the rapid replacement of B.1.160 by the alpha variant (B.1.1.7) that launched the third wave of the epidemic in February 2021. Overall, these results illustrate how the founder effect in combination with cryptic transmission, instead of repeated international introductions or higher transmissibility, can govern viral diversity. LA - English DB - MTMT ER -