@article{MTMT:34779369, title = {Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting.}, url = {https://m2.mtmt.hu/api/publication/34779369}, author = {Prosz, Aurel and Sahgal, Pranshu and Huffman, Brandon M and Sztupinszki, Zsofia and Morris, Clare X and Chen, David and Börcsök, Judit and Diossy, Miklos and Tisza, Viktoria and Spisák, Sándor and Likasitwatanakul, Pornlada and Rusz, Orsolya and Csabai, István and Cecchini, Michael and Baca, Yasmine and Elliot, Andrew and Enzinger, Peter and Singh, Harshabad and Ubellaker, Jessalyn and Lazaro, Jean-Bernard and Cleary, James M and Szállási, Zoltán and Sethi, Nilay S}, doi = {10.1038/s41698-024-00561-6}, journal-iso = {NPJ PRECIS ONCOL}, journal = {NPJ PRECISION ONCOLOGY}, volume = {8}, unique-id = {34779369}, abstract = {Homologous recombination (HR) and nucleotide excision repair (NER) are the two most frequently disabled DNA repair pathways in cancer. HR-deficient breast, ovarian, pancreatic and prostate cancers respond well to platinum chemotherapy and PARP inhibitors. However, the frequency of HR deficiency in gastric and esophageal adenocarcinoma (GEA) still lacks diagnostic and functional validation. Using whole exome and genome sequencing data, we found that a significant subset of GEA, but very few colorectal adenocarcinomas, show evidence of HR deficiency by mutational signature analysis (HRD score). High HRD gastric cancer cell lines demonstrated functional HR deficiency by RAD51 foci assay and increased sensitivity to platinum chemotherapy and PARP inhibitors. Of clinical relevance, analysis of three different GEA patient cohorts demonstrated that platinum treated HR deficient cancers had better outcomes. A gastric cancer cell line with strong sensitivity to cisplatin showed HR proficiency but exhibited NER deficiency by two photoproduct repair assays. Single-cell RNA-sequencing revealed that, in addition to inducing apoptosis, cisplatin treatment triggered ferroptosis in a NER-deficient gastric cancer, validated by intracellular GSH assay. Overall, our study provides preclinical evidence that a subset of GEAs harbor genomic features of HR and NER deficiency and may therefore benefit from platinum chemotherapy and PARP inhibitors.}, year = {2024}, eissn = {2397-768X}, orcid-numbers = {Rusz, Orsolya/0000-0001-5726-4072; Csabai, István/0000-0001-9232-9898; Szállási, Zoltán/0000-0001-5395-7509} } @article{MTMT:34599260, title = {Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses.}, url = {https://m2.mtmt.hu/api/publication/34599260}, author = {Rahman, Nadim and O'Cathail, Colman and Zyoud, Ahmad and Sokolov, Alexey and Oude Munnink, Bas and Grüning, Björn and Cummins, Carla and Amid, Clara and Nieuwenhuijse, David F and Visontai, David and Yuan, David Yu and Gupta, Dipayan and Prasad, Divyae K and Gulyás, Gábor Máté and Rinck, Gabriele and McKinnon, Jasmine and Rajan, Jeena and Knaggs, Jeff and Skiby, Jeffrey Edward and Stéger, József and Szarvas, Judit and Gueye, Khadim and Papp, Krisztián and Hoek, Maarten and Kumar, Manish and Ventouratou, Marianna A and Bouquieaux, Marie-Catherine and Koliba, Martin and Mansurova, Milena and Haseeb, Muhammad and Worp, Nathalie and Harrison, Peter W and Leinonen, Rasko and Thorne, Ross and Selvakumar, Sandeep and Hunt, Sarah and Venkataraman, Sundar and Jayathilaka, Suran and Cezard, Timothée and Maier, Wolfgang and Waheed, Zahra and Iqbal, Zamin and Aarestrup, Frank Møller and Csabai, István and Koopmans, Marion and Burdett, Tony and Cochrane, Guy}, doi = {10.1099/mgen.0.001188}, journal-iso = {MICROB GENOM}, journal = {MICROBIAL GENOMICS}, volume = {10}, unique-id = {34599260}, issn = {2057-5858}, abstract = {The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads. In this paper we describe (1) open data sharing, (2) tools for submission, analysis, visualisation and data claiming (e.g. ORCiD), (3) the systematic analysis of these datasets, at scale via the SARS-CoV-2 Data Hubs as well as (4) lessons learnt. This paper describes a component of the Platform, the SARS-CoV-2 Data Hubs, which enable the extension and set up of infrastructure that we intend to use more widely in the future for pathogen surveillance and pandemic preparedness.}, keywords = {Data sharing; Open data; COVID-19; SARS-CoV-2; Emerging variants; Genomics sequencing}, year = {2024}, eissn = {2057-5858}, orcid-numbers = {Visontai, David/0000-0002-0029-709X; Stéger, József/0000-0003-2836-1855; Papp, Krisztián/0000-0003-0619-8233; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34527502, title = {Biologically informed deep learning for explainable epigenetic clocks}, url = {https://m2.mtmt.hu/api/publication/34527502}, author = {Prosz, Aurel and Pipek, Orsolya Anna and Börcsök, Judit and Palla, Gergely and Szallasi, Zoltan and Spisák, Sándor and Csabai, István}, doi = {10.1038/s41598-023-50495-5}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {14}, unique-id = {34527502}, issn = {2045-2322}, abstract = {Ageing is often characterised by progressive accumulation of damage, and it is one of the most important risk factors for chronic disease development. Epigenetic mechanisms including DNA methylation could functionally contribute to organismal aging, however the key functions and biological processes may govern ageing are still not understood. Although age predictors called epigenetic clocks can accurately estimate the biological age of an individual based on cellular DNA methylation, their models have limited ability to explain the prediction algorithm behind and underlying key biological processes controlling ageing. Here we present XAI-AGE, a biologically informed, explainable deep neural network model for accurate biological age prediction across multiple tissue types. We show that XAI-AGE outperforms the first-generation age predictors and achieves similar results to deep learning-based models, while opening up the possibility to infer biologically meaningful insights of the activity of pathways and other abstract biological processes directly from the model.}, year = {2024}, eissn = {2045-2322}, orcid-numbers = {Pipek, Orsolya Anna/0000-0001-8109-0340; Palla, Gergely/0000-0002-3406-4200; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34525724, title = {Systematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples}, url = {https://m2.mtmt.hu/api/publication/34525724}, author = {Pipek, Orsolya Anna and Medgyes-Horváth, Anna and Stéger, József and Papp, Krisztián and Visontai, David and Koopmans, M. and Nieuwenhuijse, D. and Oude, Munnink B.B. and Cochrane, G. and Rahman, N. and Cummins, C. and Yuan, D.Y. and Selvakumar, S. and Mansurova, M. and O’Cathail, C. and Sokolov, A. and Thorne, R. and Worp, N. and Amid, C. and Csabai, István}, doi = {10.1038/s41467-023-43391-z}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {15}, unique-id = {34525724}, issn = {2041-1723}, year = {2024}, eissn = {2041-1723}, orcid-numbers = {Pipek, Orsolya Anna/0000-0001-8109-0340; Medgyes-Horváth, Anna/0000-0003-4435-5797; Stéger, József/0000-0003-2836-1855; Papp, Krisztián/0000-0003-0619-8233; Visontai, David/0000-0002-0029-709X; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34518530, title = {Annotated dataset for training deep learning models to detect astrocytes in human brain tissue}, url = {https://m2.mtmt.hu/api/publication/34518530}, author = {Olar, Alex and Tyler, Teadora and Hoppa, Paulina and Frank, Erzsébet and Csabai, István and Adorján, István and Pollner, Péter}, doi = {10.1038/s41597-024-02908-x}, journal-iso = {SCI DATA}, journal = {SCIENTIFIC DATA}, volume = {11}, unique-id = {34518530}, abstract = {Astrocytes, a type of glial cell, significantly influence neuronal function, with variations in morphology and density linked to neurological disorders. Traditional methods for their accurate detection and density measurement are laborious and unsuited for large-scale operations. We introduce a dataset from human brain tissues stained with aldehyde dehydrogenase 1 family member L1 (ALDH1L1) and glial fibrillary acidic protein (GFAP). The digital whole slide images of these tissues were partitioned into 8730 patches of 500 × 500 pixels, comprising 2323 ALDH1L1 and 4714 GFAP patches at a pixel size of 0.5019/pixel, furthermore 1382 ADHD1L1 and 311 GFAP patches at 0.3557/pixel. Sourced from 16 slides and 8 patients our dataset promotes the development of tools for glial cell detection and quantification, offering insights into their density distribution in various brain areas, thereby broadening neuropathological study horizons. These samples hold value for automating detection methods, including deep learning. Derived from human samples, our dataset provides a platform for exploring astrocyte functionality, potentially guiding new diagnostic and treatment strategies for neurological disorders.}, keywords = {Brain; Humans; metabolism; ASTROCYTES; Nervous System Diseases; neurologic disease; human; Neuroglia; pathology; Glia; ASTROCYTE; Deep learning}, year = {2024}, eissn = {2052-4463}, orcid-numbers = {Olar, Alex/0000-0001-8094-4324; Csabai, István/0000-0001-9232-9898; Pollner, Péter/0000-0003-0464-4893} } @article{MTMT:34558223, title = {FOLSAV-PÓTLÁS HATÁSÁNAK VIZSGÁLATA HYPERHOMOCYSTEINAEMIÁBAN SZENVEDŐ IBD-S BETEGEKBEN}, url = {https://m2.mtmt.hu/api/publication/34558223}, author = {Barták, Barbara Kinga and Nagy, Zoltán and Farkas, Eszter Alexandra and Bányai, F and Szakállas, Nikolett and Valcz, Gábor and Pipek, Orsolya Anna and Csabai, István and Takács, István and Molnár, Béla}, journal-iso = {MBA}, journal = {MAGYAR BELORVOSI ARCHIVUM}, volume = {76}, unique-id = {34558223}, issn = {0133-5464}, year = {2023}, pages = {300-300}, orcid-numbers = {Nagy, Zoltán/0000-0002-6493-5601; Valcz, Gábor/0000-0002-7109-3529; Pipek, Orsolya Anna/0000-0001-8109-0340; Csabai, István/0000-0001-9232-9898; Takács, István/0000-0002-7810-4833; Molnár, Béla/0000-0001-6655-7942} } @article{MTMT:34398764, title = {Nucleotide excision repair deficiency is a targetable therapeutic vulnerability in clear cell renal cell carcinoma}, url = {https://m2.mtmt.hu/api/publication/34398764}, author = {Prosz, Aurel and Duan, Haohui and Tisza, Viktoria and Sahgal, Pranshu and Topka, Sabine and Klus, Gregory T. and Börcsök, Judit and Sztupinszki, Zsofia and Hanlon, Timothy and Diossy, Miklos and Vízkeleti, Laura and Stormoen, Dag Rune and Csabai, István and Pappot, Helle and Vijai, Joseph and Offit, Kenneth and Ried, Thomas and Sethi, Nilay and Mouw, Kent W. and Spisák, Sándor and Pathania, Shailja and Szállási, Zoltán}, doi = {10.1038/s41598-023-47946-4}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34398764}, issn = {2045-2322}, abstract = {Due to a demonstrated lack of DNA repair deficiencies, clear cell renal cell carcinoma (ccRCC) has not benefitted from targeted synthetic lethality-based therapies. We investigated whether nucleotide excision repair (NER) deficiency is present in an identifiable subset of ccRCC cases that would render those tumors sensitive to therapy targeting this specific DNA repair pathway aberration. We used functional assays that detect UV-induced 6–4 pyrimidine-pyrimidone photoproducts to quantify NER deficiency in ccRCC cell lines. We also measured sensitivity to irofulven, an experimental cancer therapeutic agent that specifically targets cells with inactivated transcription-coupled nucleotide excision repair (TC-NER). In order to detect NER deficiency in clinical biopsies, we assessed whole exome sequencing data for the presence of an NER deficiency associated mutational signature previously identified in ERCC2 mutant bladder cancer. Functional assays showed NER deficiency in ccRCC cells. Some cell lines showed irofulven sensitivity at a concentration that is well tolerated by patients. Prostaglandin reductase 1 (PTGR1), which activates irofulven, was also associated with this sensitivity. Next generation sequencing data of the cell lines showed NER deficiency-associated mutational signatures. A significant subset of ccRCC patients had the same signature and high PTGR1 expression. ccRCC cell line-based analysis showed that NER deficiency is likely present in this cancer type. Approximately 10% of ccRCC patients in the TCGA cohort showed mutational signatures consistent with ERCC2 inactivation associated NER deficiency and also substantial levels of PTGR1 expression. These patients may be responsive to irofulven, a previously abandoned anticancer agent that has minimal activity in NER-proficient cells.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Vízkeleti, Laura/0000-0001-6870-3499; Csabai, István/0000-0001-9232-9898; Szállási, Zoltán/0000-0001-5395-7509} } @article{MTMT:34226088, title = {Author Correction: A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus (Nature Communications, (2023), 14, 1, (5118), 10.1038/s41467-023-40616-z)}, url = {https://m2.mtmt.hu/api/publication/34226088}, author = {Spisak, S. and Tisza, V. and Nuzzo, P.V. and Seo, J.-H. and Pataki, Bálint Ármin and Ribli, Dezső and Sztupinszki, Z. and Bell, C. and Rohanizadegan, M. and Stillman, D.R. and Alaiwi, S.A. and Bartels, A.H. and Papp, M. and Shetty, A. and Abbasi, F. and Lin, X. and Lawrenson, K. and Gayther, S.A. and Pomerantz, M. and Baca, S. and Solymosi, Norbert and Csabai, István and Szallasi, Z. and Gusev, A. and Freedman, M.L.}, doi = {10.1038/s41467-023-42515-9}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {14}, unique-id = {34226088}, issn = {2041-1723}, year = {2023}, eissn = {2041-1723}, orcid-numbers = {Solymosi, Norbert/0000-0003-1783-2041; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34117214, title = {A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus}, url = {https://m2.mtmt.hu/api/publication/34117214}, author = {Spisák, Sándor and Tisza, Viktoria and Nuzzo, P.V. and Seo, J.-H. and Pataki, Bálint Ármin and Ribli, Dezső and Sztupinszki, Z. and Bell, C. and Rohanizadegan, M. and Stillman, D.R. and Alaiwi, S.A. and Bartels, A.B. and Papp, Márton and Shetty, A. and Abbasi, F. and Lin, X. and Lawrenson, K. and Gayther, S.A. and Pomerantz, M. and Baca, S. and Solymosi, Norbert and Csabai, István and Szallasi, Z. and Gusev, A. and Freedman, M.L.}, doi = {10.1038/s41467-023-40616-z}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {14}, unique-id = {34117214}, issn = {2041-1723}, year = {2023}, eissn = {2041-1723}, orcid-numbers = {Papp, Márton/0000-0003-4975-253X; Solymosi, Norbert/0000-0003-1783-2041; Csabai, István/0000-0001-9232-9898} } @article{MTMT:34086719, title = {Annotated dataset for deep-learning-based bacterial colony detection.}, url = {https://m2.mtmt.hu/api/publication/34086719}, author = {Makrai, László and Fodróczy, Bettina and Nagy, Sára Ágnes and Czeiszing, Péter and Csabai, István and Szita, Géza and Solymosi, Norbert}, doi = {10.1038/s41597-023-02404-8}, journal-iso = {SCI DATA}, journal = {SCIENTIFIC DATA}, volume = {10}, unique-id = {34086719}, abstract = {Quantifying bacteria per unit mass or volume is a common task in various fields of microbiology (e.g., infectiology and food hygiene). Most bacteria can be grown on culture media. The unicellular bacteria reproduce by dividing into two cells, which increases the number of bacteria in the population. Methodologically, this can be followed by culture procedures, which mostly involve determining the number of bacterial colonies on the solid culture media that are visible to the naked eye. However, it is a time-consuming and laborious professional activity. Addressing the automation of colony counting by convolutional neural networks in our work, we have cultured 24 bacteria species of veterinary importance with different concentrations on solid media. A total of 56,865 colonies were annotated manually by bounding boxes on the 369 digital images of bacterial cultures. The published dataset will help developments that use artificial intelligence to automate the counting of bacterial colonies.}, year = {2023}, eissn = {2052-4463}, orcid-numbers = {Csabai, István/0000-0001-9232-9898; Solymosi, Norbert/0000-0003-1783-2041} }