Publikácie

@article{Rendek2024,

title = {Determination of the Prevalence of Microsatellite Instability, BRAF and KRAS/NRAS Mutation Status in Patients with Colorectal Cancer in Slovakia},

author = {T. Rendek and R. Saade and O. Pos and G. Kolnikova and M. Urbanova and J. Budis and L. Mihok and M. Tomas and T. Szemes and V. Repiska},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188716763&doi=10.3390%2fcancers16061128&partnerID=40&md5=6d2a917f36ffefb2b941d96e515e7a83},

doi = {10.3390/cancers16061128},

issn = {20726694},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Cancers},

volume = {16},

number = {6},

publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},

abstract = {Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease imposes, data on molecular analysis of biomarkers in CRC-diagnosed patients is scarce. In our study, we analyzed confirmed CRC patients from the database of the National Cancer Institute (NCI) and evaluated the presence of 4 biomarkers in tumor tissues. Altogether, 83 FFPE tumor tissues from CRC patients listed in the NCI database were analyzed for microsatellite instability status, presence of BRAF and KRAS/NRAS mutations, and neoplastic cell percentage in tissue samples. We identified 4 MSI-high samples, 39 KRAS/NRAS mutations, and 5 BRAF p.V600E mutations, with one case of coexistence of all three markers in a single tumor sample. We also evaluated possible relationships between biomarkers, their coexistence, and the age and sex of the studied population. © 2024 by the authors.},

keywords = {Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Holesova2024,

title = {Understanding genetic variability: exploring large-scale copy number variants through non-invasive prenatal testing in European populations},

author = {Z. Holesova and O. Pös and J. Gazdarica and M. Kucharik and J. Budis and M. Hyblova and G. Minarik and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85190362328&doi=10.1186%2fs12864-024-10267-5&partnerID=40&md5=9db9ad228e071b255f5c759790d53c82},

doi = {10.1186/s12864-024-10267-5},

issn = {14712164},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {BMC Genomics},

volume = {25},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy. In this context, a non-invasive prenatal test (NIPT) based on the sequencing of cell-free DNA (cfDNA) from pregnant women’s plasma using a low-coverage whole genome MPS (WGS) approach represents a valuable source for population studies. Here, we analyzed genomic data of 12,732 pregnant women from the Slovak (9,230), Czech (1,583), and Hungarian (1,919) populations. We identified 5,062 CNVs ranging from 200 kbp and described their basic characteristics and differences between the subject populations. Our results suggest that re-analysis of sequencing data from routine WGS assays has the potential to obtain large-scale CNV population frequencies, which are not well known and may provide valuable information to support the classification and interpretation of this type of genetic variation. Furthermore, this could contribute to expanding knowledge about the central European genome without investing in additional laboratory work, as NIPTs are a relatively widely used screening method. © The Author(s) 2024.},

keywords = {Copy number variation, Non-invasive prenatal testing, Population study},

pubstate = {published},

tppubtype = {article}

}

@article{Gazdarica2024,

title = {Insights into non-informative results from non-invasive prenatal screening through gestational age, maternal BMI, and age analyses},

author = {J. Gazdarica and N. Forgacova and T. Sladecek and M. Kucharik and J. Budis and M. Hyblova and M. Sekelska and A. Gnip and G. Minarik and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85187162464&doi=10.1371%2fjournal.pone.0280858&partnerID=40&md5=c7288799cea18fb3514ec062aa42a91f},

doi = {10.1371/journal.pone.0280858},

issn = {19326203},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {PLoS ONE},

volume = {19},

number = {3 March},

publisher = {Public Library of Science},

abstract = {The discovery of cell-free fetal DNA fragments in the maternal plasma initiated a novel testing method in prenatal care, called non-invasive prenatal screening (NIPS). One of the limitations of NIPS is the necessity for a sufficient proportion of fetal fragments in the analyzed circulating DNA mixture (fetal fraction), otherwise, the sample is uninterpretable. We present the effect of gestational age, maternal body mass index (BMI), and maternal age on the fetal fraction (FF) of the sample. We retrospectively analyzed data from 5543 pregnant women with a single male fetus who underwent NIPS from which 189 samples received a repeat testing due to an insufficient FF. We showed the relationship between the failure rate of the samples after the repeated analysis, the FF, and the gestational age at the first sampling. Next, we found that different maternal BMI categories affect the FF and thus the chance of an informative redraw. A better understanding of the factors affecting the FF will reduce the number of non-informative calls from repeated analyzes. In this study, we provide helpful information to clinicians on how to approach non-informative analyses. © 2024 Gazdarica et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},

keywords = {Aneuploidy, Cell-free nucleic acids, Prenatal diagnosis},

pubstate = {published},

tppubtype = {article}

}

@article{Bernardini2024,

title = {Alkaptonuria},

author = {G. Bernardini and D. Braconi and A. Zatkova and N. Sireau and M. J. Kujawa and W. J. Introne and O. Spiga and M. Geminiani and J. A. Gallagher and L. R. Ranganath and A. Santucci},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85187170730&doi=10.1038%2fs41572-024-00498-x&partnerID=40&md5=a17aaeee2296e31b0fabfe4fc1543b86},

doi = {10.1038/s41572-024-00498-x},

issn = {2056676X},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Nature Reviews Disease Primers},

volume = {10},

number = {1},

publisher = {Nature Research},

abstract = {Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients’ quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies. © Springer Nature Limited 2024.},

keywords = {Alkaptonuria},

pubstate = {published},

tppubtype = {article}

}

@article{Kvapilova2024,

title = {Validated WGS and WES protocols proved saliva-derived gDNA as an equivalent to blood-derived gDNA for clinical and population genomic analyses},

author = {K. Kvapilova and P. Misenko and J. Radvanszky and O. Brzon and J. Budis and J. Gazdarica and O. Pos and M. Korabecna and M. Kasny and T. Szemes and P. Kvapil and J. Paces and Z. Kozmik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185401063&doi=10.1186%2fs12864-024-10080-0&partnerID=40&md5=005d098ebc4c002ab39a2a6b70f9512d},

doi = {10.1186/s12864-024-10080-0},

issn = {14712164},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {BMC Genomics},

volume = {25},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: Whole exome sequencing (WES) and whole genome sequencing (WGS) have become standard methods in human clinical diagnostics as well as in population genomics (POPGEN). Blood-derived genomic DNA (gDNA) is routinely used in the clinical environment. Conversely, many POPGEN studies and commercial tests benefit from easy saliva sampling. Here, we evaluated the quality of variant call sets and the level of genotype concordance of single nucleotide variants (SNVs) and small insertions and deletions (indels) for WES and WGS using paired blood- and saliva-derived gDNA isolates employing genomic reference-based validated protocols. Methods: The genomic reference standard Coriell NA12878 was repeatedly analyzed using optimized WES and WGS protocols, and data calls were compared with the truth dataset published by the Genome in a Bottle Consortium. gDNA was extracted from the paired blood and saliva samples of 10 participants and processed using the same protocols. A comparison of paired blood–saliva call sets was performed in the context of WGS and WES genomic reference-based technical validation results. Results: The quality pattern of called variants obtained from genomic-reference-based technical replicates correlates with data calls of paired blood–saliva-derived samples in all levels of tested examinations despite a higher rate of non-human contamination found in the saliva samples. The F1 score of 10 blood-to-saliva-derived comparisons ranged between 0.8030–0.9998 for SNVs and between 0.8883–0.9991 for small-indels in the case of the WGS protocol, and between 0.8643–0.999 for SNVs and between 0.7781–1.000 for small-indels in the case of the WES protocol. Conclusion: Saliva may be considered an equivalent material to blood for genetic analysis for both WGS and WES under strict protocol conditions. The accuracy of sequencing metrics and variant-detection accuracy is not affected by choosing saliva as the gDNA source instead of blood but much more significantly by the genomic context, variant types, and the sequencing technology used. © The Author(s) 2024.},

keywords = {Single nucleotide variants, Validation},

pubstate = {published},

tppubtype = {article}

}

@article{Planý2023,

title = {Evaluation of bacterial consortia associated with dairy fermentation by ribosomal RNA (rrn) operon metabarcoding strategy using MinION device},

author = {M. Planý and J. Sitarčík and J. Pavlović and J. Budiš and J. Koreňová and T. Kuchta and D. Pangallo},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85144644933&doi=10.1016%2fj.fbio.2022.102308&partnerID=40&md5=605398b6214907690cf00209ead1a317},

doi = {10.1016/j.fbio.2022.102308},

issn = {22124292},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Food Bioscience},

volume = {51},

publisher = {Elsevier Ltd},

abstract = {The ability of the third generation sequencing technologies to provide longer sequence reads contributes to the use of the longest possible amplicons as specific bacterial markers for metabarcoding studies. Nanopore sequencing technologies are increasingly used worldwide to profile microbiomes in environmental and food samples. The identification of beneficial or pathogenic bacteria in dairy fermented foods is related to their valuable health properties and also contributes to food safety issues. Here we described and optimised a PCR-based methodology of almost the entire ribosomal operon sequences (16S-ITS-23S) and their subsequent sequencing by MinION device. We used three different sequencing data processing and analysis strategies. Two of those utilized user-friendly software without the need of being conversant with any programming language. We tested all workflows on a simple mock community composed of a mixture of 7 bacterial DNA. Our scripted bioinformatics pipeline denoted as “AEROS”, representing an approach based on taxonomic classification with our reference database called AEROS-DB (Almost Entire Ribosomal Operon Sequences), was applied to traditional Slovak sheep cheese made from unpasteurized milk. All bacterial genera included in the mock community were detected with relatively small differences compared to the expected relative abundance using each of the three approaches. The AEROS approach provided more accurate composition data on this community at the species level as well. The results suggested that the use of almost entire rrn operon sequences in metabarcoding studies is suitable to analyze the bacterial consortia in cheeses and related dairy fermented products. © 2022 Elsevier Ltd},

keywords = {Bacteria, Food microbiome, Nanopore},

pubstate = {published},

tppubtype = {article}

}

@article{Forgacova2023,

title = {Evaluation and limitations of different approaches among COVID-19 fatal cases using whole-exome sequencing data},

author = {N. Forgacova and Z. Holesova and R. Hekel and T. Sedlackova and Z. Pos and L. Krivosikova and P. Janega and K. M. Kuracinova and P. Babal and P. Radvak and J. Radvanszky and J. Gazdarica and J. Budis and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146101670&doi=10.1186%2fs12864-022-09084-5&partnerID=40&md5=d25846b50ef1ee4668a13ebd7d02bb47},

doi = {10.1186/s12864-022-09084-5},

issn = {14712164},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {BMC Genomics},

volume = {24},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: COVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19. Results: We selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations. Conclusions: Although our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing. © 2023, The Author(s).},

note = {cited By 0},

keywords = {Non-invasive prenatal testing, Sars-cov-2},

pubstate = {published},

tppubtype = {article}

}

@article{Klimova2023,

title = {Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as a cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro},

author = {D. Klimova and J. Jakubechova and U. Altanerova and A. Nicodemou and J. Styk and T. Szemes and V. Repiska and C. Altaner},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85147104802&doi=10.1016%2fj.mcp.2023.101894&partnerID=40&md5=bd0eb370c53359ac5e12f26b2fbea314},

doi = {10.1016/j.mcp.2023.101894},

issn = {08908508},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Molecular and Cellular Probes},

volume = {67},

publisher = {Academic Press},

abstract = {Extracellular vesicles (EVs) are nowadays a target of interest in cancer therapy as a successful drug delivering tool. Based on their many beneficial biocompatible properties are designed to transport nucleic acids, proteins, various nanomaterials or chemotherapeutics. Extracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) possess their tumor-homing abilities. This inspired us to engineer the MSC's EVs to be packed with chemotherapeutic agents and deliver it as a Trojan horse directly into tumor cells. In our study, human dental pulp MSCs (DP-MSCs) were cultivated with gemcitabine (GCB), which led to its absorption by the cells and subsequent secretion of the drug out into conditioned media in EVs. Concentrated conditioned media containing small EVs (potentially exosomes) significantly inhibited the cell growth of pancreatic carcinoma cell lines in vitro. DP-MSCs were simultaneously engineered to express a suicide gene fused yeast cytosinedeaminase:uracilphosphoribosyltransferase (yCD::UPRT). The product of the suicide gene converts non-toxic prodrug 5-fluorocytosine (5-FC) to highly cytotoxic chemotherapeutic drug 5-fluorouracil (5-FU) in the recipient cancer cells. Conversion of 5-FC to 5-FU had an additional effect on cancer cell's growth inhibition. Our results showed a therapeutic potential for DP-MSC-EVs to be designed for successful delivering of chemotherapeutic drugs, together with prodrug suicide gene therapy system. © 2023 The Author(s)},

keywords = {Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Styk2023,

title = {Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook},

author = {J. Styk and Z. Pös and O. Pös and J. Radvanszky and E. H. Turnova and G. Buglyó and D. Klimova and J. Budis and V. Repiska and B. Nagy and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146857319&doi=10.1007%2fs13167-023-00312-w&partnerID=40&md5=3b63e993459e80e985772551f60bbc4e},

doi = {10.1007/s13167-023-00312-w},

issn = {18785077},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {EPMA Journal},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {A form of genomic alteration called microsatellite instability (MSI) occurs in a class of tandem repeats (TRs) called microsatellites (MSs) or short tandem repeats (STRs) due to the failure of a post-replicative DNA mismatch repair (MMR) system. Traditionally, the strategies for determining MSI events have been low-throughput procedures that typically require assessment of tumours as well as healthy samples. On the other hand, recent large-scale pan-tumour studies have consistently highlighted the potential of massively parallel sequencing (MPS) on the MSI scale. As a result of recent innovations, minimally invasive methods show a high potential to be integrated into the clinical routine and delivery of adapted medical care to all patients. Along with advances in sequencing technologies and their ever-increasing cost-effectiveness, they may bring about a new era of Predictive, Preventive and Personalised Medicine (3PM). In this paper, we offered a comprehensive analysis of high-throughput strategies and computational tools for the calling and assessment of MSI events, including whole-genome, whole-exome and targeted sequencing approaches. We also discussed in detail the detection of MSI status by current MPS blood-based methods and we hypothesised how they may contribute to the shift from conventional medicine to predictive diagnosis, targeted prevention and personalised medical services. Increasing the efficacy of patient stratification based on MSI status is crucial for tailored decision-making. Contextually, this paper highlights drawbacks both at the technical level and those embedded deeper in cellular/molecular processes and future applications in routine clinical testing. © 2023, The Author(s).},

keywords = {Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Holesova2023,

title = {Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies},

author = {Z. Holesova and L. Krasnicanova and R. Saade and O. Pös and J. Budis and J. Gazdarica and V. Repiska and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85151112952&doi=10.3390%2fgenes14030715&partnerID=40&md5=d89df2608717b306d353873f39018ecb},

doi = {10.3390/genes14030715},

issn = {20734425},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Genes},

volume = {14},

number = {3},

publisher = {MDPI},

abstract = {Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field. © 2023 by the authors.},

keywords = {Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Artimová2023,

title = {Microbial Communities on Samples of Commercially Available Fresh-Consumed Leafy Vegetables and Small Berries},

author = {R. Artimová and M. Játiová and J. Baumgartnerová and N. Lipková and J. Petrová and J. Maková and S. Javoreková and L. Hleba and J. Medová and J. Medo},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149063046&doi=10.3390%2fhorticulturae9020150&partnerID=40&md5=e3ba1bfcd4f74a841455e98c9dedf4dc},

doi = {10.3390/horticulturae9020150},

issn = {23117524},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Horticulturae},

volume = {9},

number = {2},

publisher = {MDPI},

abstract = {Microbial communities on fresh-consumed plant products are an important predictor of quality and safety for the consumer. Totally, 45 samples of berry fruits (8 blackberries, 9 blueberries, 8 strawberries, 8 raspberries, 12 currants) and 40 samples of leafy vegetables (20 lettuce, 6 cornsalad, 8 rocket, 8 spinach) were analyzed using cultivation and DNA-depended methods. Total aerobic count, coliforms, and yeasts were significantly lower in fruits while counts of filamentous fungi were similar. Pantoea, Enterobacter, and Klebsiella were the most common colonies grown on VRBL agar. Salmonella was detected in single sample of cornsalad using qPCR but no sample contained Escherichia coli harboring stx1, stx2 and intimin genes. Sequencing of V4 region of bacteria 16S rRNA and ITS2 region of fungi amplified from plant tissue-extracted DNA confirmed different composition of fruit and vegetable microbiome. Pre-enrichment of bacteria in phosphate buffered water allowed deeper analysis of Enterobacteriaceae using V4–V5 region of 16S rRNA while differences among communities were described similarly. Pantoea, Klebsiella, or Staphylococcus were more frequent in berries while Pseudomonas, Flavobacterium, or Sphingobacterium in leafy vegetables. Comparison of inner and outer leaves of head-forming lettuces (6 iceberg, 5 romain) showed that outer leaves are colonized by more bacteria with higher diversity. Microbiological safety of fresh production requires more attention as the potentially pathogenic bacteria were detected, particularly in leafy vegetables. However, the true pathogenicity of such bacteria needs further research. © 2023 by the authors.},

keywords = {Bacteria, Food microbiome},

pubstate = {published},

tppubtype = {article}

}

@article{Pos2023351,

title = {APOC3 and ABCA1 variants in unusual combined hypolipidaemia showing premature peripheral vascular disease},

author = {Z. Pos and M. Khedr and J. Radvanszky and A. Penesova and R. Hekel and T. Szemes and L. R. Ranganath and A. Zatkova},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152244379&doi=10.4149%2fBLL_2023_053&partnerID=40&md5=9608504946b889c84bdb8421b1c8333f},

doi = {10.4149/BLL_2023_053},

issn = {00069248},

year  = {2023},

date = {2023-01-01},

journal = {Bratislava Medical Journal},

volume = {124},

number = {5},

pages = {351-355},

publisher = {Comenius University in Bratislava},

abstract = {BACKGROUND: Familial combined hypolipidaemia is a condition characterised by very low concentrations of circulating very-low-density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL), and highdensity lipoprotein cholesterol (HDL). It is thought that low LDL/combined hypolipidaemia can protect from cardiovascular disease (CVD), but this is not what we found in a case we present. OBJECTIVE: We report on a 57-years-old male patient with combined hypolipidaemia who presented with premature peripheral vascular disease. We investigated also his two sons, 32 and 27-years-old, who manifested a tendency to low lipid levels. METHODS AND RESULTS: We used Illumina exome analysis in all three individuals and in all of them we could exclude the major effect of the variants within the genes most frequently mutated in hypolipidaemia, including recently reported LIPC gene variant. Instead, in all three individuals we identifi ed a novel ABCA1 variant, possibly responsible for the decreased HDL levels. The proband and one of his sons also share the splicing APOC3 variant rs138326449, known to be associated with decreased TG levels. CONCLUSION: The heterogeneous nature and the risk of atherosclerosis in combined hypolipidaemia seems to be variable, based on an interplay between low HDL and LDL levels, and it depends on the combination of variants that cause it (Tab. 2, Ref. 38). Text in PDF www.elis.sk © 2023, Bratislava Medical Journal. All Rights Reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sládeček2023,

title = {Combination of expert guidelines-based and machine learning-based approaches leads to superior accuracy of automated prediction of clinical effect of copy number variations},

author = {T. Sládeček and M. Gažiová and M. Kucharík and A. Zaťková and Z. Pös and O. Pös and W. Krampl and E. Tomková and M. Hýblová and G. Minárik and J. Radvánszky and J. Budiš and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85163886010&doi=10.1038%2fs41598-023-37352-1&partnerID=40&md5=9752e9d83f2d1eca8a028bdffc3fd1f8},

doi = {10.1038/s41598-023-37352-1},

issn = {20452322},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Scientific Reports},

volume = {13},

number = {1},

publisher = {Nature Research},

abstract = {Clinical interpretation of copy number variants (CNVs) is a complex process that requires skilled clinical professionals. General recommendations have been recently released to guide the CNV interpretation based on predefined criteria to uniform the decision process. Several semiautomatic computational methods have been proposed to recommend appropriate choices, relieving clinicians of tedious searching in vast genomic databases. We have developed and evaluated such a tool called MarCNV and tested it on CNV records collected from the ClinVar database. Alternatively, the emerging machine learning-based tools, such as the recently published ISV (Interpretation of Structural Variants), showed promising ways of even fully automated predictions using broader characterization of affected genomic elements. Such tools utilize features additional to ACMG criteria, thus providing supporting evidence and the potential to improve CNV classification. Since both approaches contribute to evaluation of CNVs clinical impact, we propose a combined solution in the form of a decision support tool based on automated ACMG guidelines (MarCNV) supplemented by a machine learning-based pathogenicity prediction (ISV) for the classification of CNVs. We provide evidence that such a combined approach is able to reduce the number of uncertain classifications and reveal potentially incorrect classifications using automated guidelines. CNV interpretation using MarCNV, ISV, and combined approach is available for non-commercial use at https://predict.genovisio.com/ . © 2023, The Author(s).},

keywords = {Computational method, Copy number variation},

pubstate = {published},

tppubtype = {article}

}

@article{Gombos2023,

title = {New Possible Ways to Use Exosomes in Diagnostics and Therapy via JAK/STAT Pathways},

author = {G. Gombos and N. Németh and O. Pös and J. Styk and G. Buglyó and T. Szemes and L. Danihel and B. Nagy and I. Balogh and B. Soltész},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85166312107&doi=10.3390%2fpharmaceutics15071904&partnerID=40&md5=8119a1ec26b631331ccfdf1c587355e5},

doi = {10.3390/pharmaceutics15071904},

issn = {19994923},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Pharmaceutics},

volume = {15},

number = {7},

publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},

abstract = {Exosomes have the potential to be the future of personalized diagnostics and therapy. They are nano-sized particles between 30 and 100 nm flowing in the extracellular milieu, where they mediate cell–cell communication and participate in immune system regulation. Tumor-derived exosomes (TDEs) secreted from different types of cancer cells are the key regulators of the tumor microenvironment. With their immune suppressive cargo, TDEs prevent the antitumor immune response, leading to reduced effectiveness of cancer treatment by promoting a pro-tumorigenic microenvironment. Involved signaling pathways take part in the regulation of tumor proliferation, differentiation, apoptosis, and angiogenesis. Signal transducers and activators of transcription factors (STATs) and Janus kinase (JAK) signaling pathways are crucial in malignancies and autoimmune diseases alike, and their potential to be manipulated is currently the focus of interest. In this review, we aim to discuss exosomes, TDEs, and the JAK/STAT pathways, along with mediators like interleukins, tripartite motif proteins, and interferons. © 2023 by the authors.},

keywords = {Exosomes},

pubstate = {published},

tppubtype = {article}

}

@article{Pös2023,

title = {Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer},

author = {O. Pös and J. Styk and G. Buglyó and M. Zeman and L. Lukyova and K. Bernatova and E. Hrckova Turnova and T. Rendek and Á. Csók and V. Repiska and B. Nagy and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164844125&doi=10.3390%2fijms241310520&partnerID=40&md5=7a3be1fd203bc9e0cf04f84a8bbfe4de},

doi = {10.3390/ijms241310520},

issn = {16616596},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {13},

publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},

abstract = {Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile. © 2023 by the authors.},

keywords = {Gut microbiome, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Baláž2023,

title = {PHERI—Phage Host ExploRation Pipeline},

author = {A. Baláž and M. Kajsik and J. Budiš and T. Szemes and J. Turňa},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164160201&doi=10.3390%2fmicroorganisms11061398&partnerID=40&md5=0a09643955666b6b600356ced3043434},

doi = {10.3390/microorganisms11061398},

issn = {20762607},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Microorganisms},

volume = {11},

number = {6},

publisher = {MDPI},

abstract = {Antibiotic resistance is becoming a common problem in medicine, food, and industry, with multidrug-resistant bacterial strains occurring in all regions. One of the possible future solutions is the use of bacteriophages. Phages are the most abundant form of life in the biosphere, so we can highly likely purify a specific phage against each target bacterium. The identification and consistent characterization of individual phages was a common form of phage work and included determining bacteriophages’ host-specificity. With the advent of new modern sequencing methods, there was a problem with the detailed characterization of phages in the environment identified by metagenome analysis. The solution to this problem may be to use a bioinformatic approach in the form of prediction software capable of determining a bacterial host based on the phage whole-genome sequence. The result of our research is the machine learning algorithm-based tool called PHERI. PHERI predicts the suitable bacterial host genus for the purification of individual viruses from different samples. In addition, it can identify and highlight protein sequences that are important for host selection. © 2023 by the authors.},

keywords = {Bacteriophages, Computational method},

pubstate = {published},

tppubtype = {article}

}

@article{Sitarčík2023,

title = {WarpSTR: Determining tandem repeat lengths using raw nanopore signals},

author = {J. Sitarčík and T. Vinař and B. Brejová and W. Krampl and J. Budiš and J. Radvánszky and M. Lucká},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164065703&doi=10.1093%2fbioinformatics%2fbtad388&partnerID=40&md5=f1f1f8d8f94b30843c974abbde7ed2ce},

doi = {10.1093/bioinformatics/btad388},

issn = {13674803},

year  = {2023},

date = {2023-01-01},

journal = {Bioinformatics},

volume = {39},

number = {6},

publisher = {Oxford University Press},

abstract = {Motivation: Short tandem repeats (STRs) are regions of a genome containing many consecutive copies of the same short motif, possibly with small variations. Analysis of STRs has many clinical uses but is limited by technology mainly due to STRs surpassing the used read length. Nanopore sequencing, as one of long-read sequencing technologies, produces very long reads, thus offering more possibilities to study and analyze STRs. Basecalling of nanopore reads is however particularly unreliable in repeating regions, and therefore direct analysis from raw nanopore data is required. Results: Here, we present WarpSTR, a novel method for characterizing both simple and complex tandem repeats directly from raw nanopore signals using a finite-state automaton and a search algorithm analogous to dynamic time warping. By applying this approach to determine the lengths of 241 STRs, we demonstrate that our approach decreases the mean absolute error of the STR length estimate compared to basecalling and STRique. © 2023 The Author(s). Published by Oxford University Press.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rešková2023177,

title = {Molecular characterization of Escherichia coli isolated from hemp seeds},

author = {Z. Rešková and M. Andrezál and H. Drahovská and T. Szemes and T. Kuchta},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85161933814&partnerID=40&md5=26f0023f29f92cfa78b356226118f466},

issn = {13368672},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Journal of Food and Nutrition Research},

volume = {62},

number = {2},

pages = {177-182},

publisher = {Food Reseach Institute},

abstract = {Summary Hemp seeds are increasingly produced on small farms in Slovakia and used for production of food. We detected contamination of 1.4 × 107 CFU·g-1 coliform bacteria in hemp seeds from a small farm and isolated three strains of Escherichia coli. These were characterized by GTG-typing and by whole genome sequencing. The three strains were indistinguishable from each other by GTG-typing but different from a reference strain E. coli CCM 2024. They were not distinguished either by multi-locus sequence type (MLST) deduced from whole genome sequences, as all strains were of sequence type 58, or by core genome-based MLST (cgMLST), as all strains belonged to type 148521. All strains were found to be fumC4/fimH32 type and serotype H21, O-antigen was not identified. No plasmid origin was detected. No gene encoding for shiga toxin was detected. Several virulence-associated genes were detected in all three strains at high identities with sequences in the database, namely, fimH, lpfA, terC, csgA, hlyE, nlpI, yehB, yehC and yehD. Further virulence-associated genes were detected at shorter lengths, namely, fdeC, gad and yehA. Several antibiotic resistance genes were also identified. The strains were found to be virtually identical. With a probability of being a human pathogen, they need to be addressed for on-farm food production safety. © 2023 National Agricultural and Food Centre (Slovakia).},

keywords = {Bacteria},

pubstate = {published},

tppubtype = {article}

}

@article{Budiš2023,

title = {SnakeLines: integrated set of computational pipelines for sequencing reads},

author = {J. Budiš and W. Krampl and M. Kucharík and R. Hekel and A. Goga and J. Sitarčík and M. Lichvár and D. Smol'ak and M. Böhmer and A. Baláž and F. Ďuriš and J. Gazdarica and K. Šoltys and J. Turňa and J. Radvánszky and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85179214150&doi=10.1515%2fjib-2022-0059&partnerID=40&md5=d6176bc0c7158cc8f4a5ee6fd000bbca},

doi = {10.1515/jib-2022-0059},

issn = {16134516},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Journal of integrative bioinformatics},

volume = {20},

number = {3},

abstract = {With the rapid growth of massively parallel sequencing technologies, still more laboratories are utilising sequenced DNA fragments for genomic analyses. Interpretation of sequencing data is, however, strongly dependent on bioinformatics processing, which is often too demanding for clinicians and researchers without a computational background. Another problem represents the reproducibility of computational analyses across separated computational centres with inconsistent versions of installed libraries and bioinformatics tools. We propose an easily extensible set of computational pipelines, called SnakeLines, for processing sequencing reads; including mapping, assembly, variant calling, viral identification, transcriptomics, and metagenomics analysis. Individual steps of an analysis, along with methods and their parameters can be readily modified in a single configuration file. Provided pipelines are embedded in virtual environments that ensure isolation of required resources from the host operating system, rapid deployment, and reproducibility of analysis across different Unix-based platforms. SnakeLines is a powerful framework for the automation of bioinformatics analyses, with emphasis on a simple set-up, modifications, extensibility, and reproducibility. The framework is already routinely used in various research projects and their applications, especially in the Slovak national surveillance of SARS-CoV-2. © 2023 the author(s), published by De Gruyter, Berlin/Boston.},

keywords = {Computational pipeline},

pubstate = {published},

tppubtype = {article}

}

@article{Gromova2023,

title = {The effect of plasma-activated water in a mouse model of inflammatory bowel disease},

author = {B. Gromova and B. Konecna and M. Suchonova and S. Pasztor and P. Celec and L. Tothova and M. Lichvar and J. Budis and J. Radvanszky and D. Rusnakova and T. Szemes and Z. Machala and R. Gardlik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85160071712&doi=10.1002%2fppap.202300053&partnerID=40&md5=bd251feb6cc3883a722e4cee94b96851},

doi = {10.1002/ppap.202300053},

issn = {16128850},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Plasma Processes and Polymers},

volume = {20},

number = {9},

publisher = {John Wiley and Sons Inc},

abstract = {Inflammatory bowel disease (IBD) is a group of disorders with complex pathogenesis, including oxidative stress and microbial dysbiosis. The aim of this study was to analyze the effect of intracolonic administration of plasma-activated water (PAW) on the oxidative status and gut microbiota diversity in the colon of healthy mice and mice with IBD. Interestingly, PAW increased oxidative stress markers in the colon tissue, and this effect was more pronounced in IBD mice. Our results show that PAW increases microbial diversity in a healthy gut and decreases it in an inflamed gut. We conclude that the effect of PAW is bidirectional and depends on the underlying condition. Our findings do not support the proposed therapeutic potential of PAW in IBD. © 2023 Wiley-VCH GmbH.},

keywords = {Gut microbiome},

pubstate = {published},

tppubtype = {article}

}

@article{Radvánszka2022,

title = {Sequential development of several RT-qPCR tests using LNA nucleotides and dual probe technology to differentiate SARS-CoV-2 from influenza A and B},

author = {M. Radvánszka and E. D. Paul and R. Hajdu and K. Boršová and V. Kováčová and P. Putaj and S. Bírová and I. Čirková and M. Čarnecký and K. Buranovská and A. Szobi and N. Vojtaššáková and D. Drobná and V. Čabanová and M. Sláviková and M. Ličková and V. Vaňová and S. Fumačová Havlíková and Ľ. Lukáčiková and I. Kajanová and J. Koči and D. Rusňáková and T. Sedláčková and K. E. A. Max and T. Tuschl and T. Szemes and B. Klempa and P. Čekan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126870587&doi=10.1111%2f1751-7915.14031&partnerID=40&md5=6bfbb30ff38aa6d088d9ffd526e1762f},

doi = {10.1111/1751-7915.14031},

issn = {17517907},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Microbial Biotechnology},

publisher = {John Wiley and Sons Ltd},

abstract = {Sensitive and accurate RT-qPCR tests are the primary diagnostic tools to identify SARS-CoV-2-infected patients. While many SARS-CoV-2 RT-qPCR tests are available, there are significant differences in test sensitivity, workflow (e.g. hands-on-time), gene targets and other functionalities that users must consider. Several publicly available protocols shared by reference labs and public health authorities provide useful tools for SARS-CoV-2 diagnosis, but many have shortcomings related to sensitivity and laborious workflows. Here, we describe a series of SARS-CoV-2 RT-qPCR tests that are originally based on the protocol targeting regions of the RNA-dependent RNA polymerase (RdRp) and envelope (E) coding genes developed by the Charité Berlin. We redesigned the primers/probes, utilized locked nucleic acid nucleotides, incorporated dual probe technology and conducted extensive optimizations of reaction conditions to enhance the sensitivity and specificity of these tests. By incorporating an RNase P internal control and developing multiplexed assays for distinguishing SARS-CoV-2 and influenza A and B, we streamlined the workflow to provide quicker results and reduced consumable costs. Some of these tests use modified enzymes enabling the formulation of a room temperature-stable master mix and lyophilized positive control, thus increasing the functionality of the test and eliminating cold chain shipping and storage. Moreover, a rapid, RNA extraction-free version enables high sensitivity detection of SARS-CoV-2 in about an hour using minimally invasive, self-collected gargle samples. These RT-qPCR assays can easily be implemented in any diagnostic laboratory and can provide a powerful tool to detect SARS-CoV-2 and the most common seasonal influenzas during the vaccination phase of the pandemic. © 2022 Multiplex DX, S.R.O. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.},

keywords = {Sars-cov-2, Viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Soltész2022,

title = {The role of exosomes in cancer progression},

author = {B. Soltész and G. Buglyó and N. Németh and M. Szilágyi and O. Pös and T. Szemes and I. Balogh and B. Nagy},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85121366077&doi=10.3390%2fijms23010008&partnerID=40&md5=a6c0cdd2a0624326aa4378c4af43611b},

doi = {10.3390/ijms23010008},

issn = {16616596},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

number = {1},

publisher = {MDPI},

abstract = {Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non‐invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell‐to‐cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next‐generation treatment of cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Gažiová2022,

title = {Automated prediction of the clinical impact of structural copy number variations},

author = {M. Gažiová and T. Sládeček and O. Pös and M. Števko and W. Krampl and Z. Pös and R. Hekel and M. Hlavačka and M. Kucharík and J. Radvánszky and J. Budiš and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85122796228&doi=10.1038%2fs41598-021-04505-z&partnerID=40&md5=2826a9187c8d22af2fdc6f5d22911cf2},

doi = {10.1038/s41598-021-04505-z},

issn = {20452322},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Scientific Reports},

volume = {12},

number = {1},

publisher = {Nature Research},

abstract = {Copy number variants (CNVs) play an important role in many biological processes, including the development of genetic diseases, making them attractive targets for genetic analyses. The interpretation of the effect of these structural variants is a challenging problem due to highly variable numbers of gene, regulatory, or other genomic elements affected by the CNV. This led to the demand for the interpretation tools that would relieve researchers, laboratory diagnosticians, genetic counselors, and clinical geneticists from the laborious process of annotation and classification of CNVs. We designed and validated a prediction method (ISV; Interpretation of Structural Variants) that is based on boosted trees which takes into account annotations of CNVs from several publicly available databases. The presented approach achieved more than 98% prediction accuracy on both copy number loss and copy number gain variants while also allowing CNVs being assigned “uncertain” significance in predictions. We believe that ISV’s prediction capability and explainability have a great potential to guide users to more precise interpretations and classifications of CNVs. © 2022, The Author(s).},

keywords = {Computational method, Copy number variation, Variant interpretation},

pubstate = {published},

tppubtype = {article}

}

@article{Cibulka2022,

title = {Alzheimer’s Disease-Associated SNP rs708727 in SLC41A1 May Increase Risk for Parkinson’s Disease: Report from Enlarged Slovak Study},

author = {M. Cibulka and M. Brodnanova and M. Grendar and J. Necpal and J. Benetin and V. Han and E. Kurca and V. Nosal and M. Skorvanek and B. Vesely and A. Stanclova and Z. Lasabova and Z. Pös and T. Szemes and S. Stuchlik and M. Grofik and M. Kolisek},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123515600&doi=10.3390%2fijms23031604&partnerID=40&md5=009dc372f51fed5ec11f299d743865bc},

doi = {10.3390/ijms23031604},

issn = {16616596},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

number = {3},

publisher = {MDPI},

abstract = {SLC41A1 (A1) SNPs rs11240569 and rs823156 are associated with altered risk for Parkinson’s disease (PD), predominantly in Asian populations, and rs708727 has been linked to Alzheimer’s disease (AD). In this study, we have examined a potential association of the three aforementioned SNPs and of rs9438393, rs56152218, and rs61822602 (all three lying in the A1 promoter region) with PD in the Slovak population. Out of the six tested SNPs, we have identified only rs708727 as being associated with an increased risk for PD onset in Slovaks. The minor allele (A) in rs708727 is associated with PD in dominant and completely over-dominant genetic models (ORD = 1.36 (1.05–1.77)},

keywords = {Single nucleotide variants},

pubstate = {published},

tppubtype = {article}

}

@article{Buglyó2022,

title = {Liquid Biopsy as a Source of Nucleic Acid Biomarkers in the Diagnosis and Management of Lynch Syndrome},

author = {G. Buglyó and J. Styk and O. Pös and Á. Csók and V. Repiska and B. Soltész and T. Szemes and B. Nagy},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128130388&doi=10.3390%2fijms23084284&partnerID=40&md5=b115dc9efc5482690694163145c4f23e},

doi = {10.3390/ijms23084284},

issn = {16616596},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

number = {8},

publisher = {MDPI},

abstract = {Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition disorder, which may manifest as colorectal cancer (CRC), endometrial cancer (EC) or other malignancies of the gastrointestinal and genitourinary tract as well as the skin and brain. Its genetic cause is a defect in one of the four key DNA mismatch repair (MMR) loci. Testing of patients at risk is currently based on the absence of MMR protein staining and detection of mutations in cancer tissue and the germline, microsatellite instability (MSI) and the hypermethylated state of the MLH1 promoter. If LS is shown to have caused CRC, lifetime follow-up with regular screening (most importantly, colonoscopy) is required. In recent years, DNA and RNA markers extracted from liquid biopsies have found some use in the clinical diagnosis of LS. They have the potential to greatly enhance the efficiency of the follow-up process by making it minimally invasive, reproducible, and time effective. Here, we review markers reported in the literature and their current clinical applications, and we comment on possible future directions. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Martin2022326,

title = {Is amniopatch an effective treatment for spontaneous previable premature rupture of membranes? Analysis of perinatal outcome},

author = {A. Martin and P. Peter and K. Marian and G. Martin and F. Michaela and G. Juraj and F. Vladimir},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128252418&doi=10.4149%2fBLL_2022_051&partnerID=40&md5=736a5f5aed0703f708339d6c601723f7},

doi = {10.4149/BLL_2022_051},

issn = {00069248},

year  = {2022},

date = {2022-01-01},

journal = {Bratislava Medical Journal},

volume = {123},

number = {5},

pages = {326-333},

publisher = {Comenius University in Bratislava},

abstract = {OBJECTIVES: To characterize the perinatal outcomes of pregnancies complicated by spontaneous previable premature rupture of membranes with a therapeutic intervention in the form of amniopatch (AP) at the 2nd Department of Obstetrics and Gynecology (2008‒2019). MATERIALS AND METHODS: The retrospective analysis of perinatal markers and early neonatal morbidity of pregnancies treated with amniopatch. Discussion comparison with the published papers of cases of spontaneous previable rupture of membranes managed expectantly. RESULTS: Out of the total number of pregnancies, 53 met the exclusion criteria, of which 35 were terminated by delivering a live newborn, 3 newborns died during the hospitalization. The following incidence of early complications has been reported in live births: 1) Bronchopulmonary dysplasia (10/35–28.57 %), 2) Newborn respiratory distress syndrome (25/35–71.42 %), 3) Neonatal sepsis (15/35–42.85 %), 4) Intraventricular hemorrhage (14/35–40 %), 5) Periventricular leukomalacia (3/35–8.57 %), 6). Necrotizing enterocolitis (2/35– 5.71 %), 7) Retinopathy of prematurity (7/35–20 %) and 8) Foetal compression syndrome (16/35–45.71 %). In a discussion comparison with available publications of expectantly managed pregnancies, we observed a statistically signifi cantly lower incidence of respiratory distress syndrome, retinopathy, and chorioamnionitis in our cohort along with a higher incidence of foetal compression defects. CONCLUSION: Amniopatch can be a therapeutic method for reducing the neonatal mortality associated with RDS, maternal infectious morbidity, and an alternative in patients, who require an active approach to such a compromised pregnancy (Tab. 12, Fig. 1, Ref. 50). Text in PDF www.elis.sk © 2022. Bratislava Medical Journal. All Rights Reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Styk2022,

title = {Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer},

author = {J. Styk and G. Buglyó and O. Pös and Á. Csók and B. Soltész and P. Lukasz and V. Repiská and B. Nagy and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85136586949&doi=10.3390%2fcancers14153712&partnerID=40&md5=c1693e930ca57ea69fb9f5147e1de219},

doi = {10.3390/cancers14153712},

issn = {20726694},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cancers},

volume = {14},

number = {15},

publisher = {MDPI},

abstract = {Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management. © 2022 by the authors.},

keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Forgacova2022,

title = {Non-intuitive trends of fetal fraction development related to gestational age and fetal gender, and their practical implications for non-invasive prenatal testing},

author = {N. Forgacova and J. Gazdarica and J. Budis and M. Kucharik and M. Sekelska and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141451340&doi=10.1016%2fj.mcp.2022.101870&partnerID=40&md5=5f0a0eeb4603486d4288fc56950e00fe},

doi = {10.1016/j.mcp.2022.101870},

issn = {08908508},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Molecular and Cellular Probes},

volume = {66},

publisher = {Academic Press},

abstract = {Discovery of fetal cell-free DNA fragments in maternal blood revolutionized prenatal diagnostics. Although non-invasive prenatal testing (NIPT) is already a matured screening test with high specificity and sensitivity, the accurate estimation of the proportion of fetal fragments, called fetal fraction, is crucial to avoid false-negative results. In this study, we collected 6999 samples from women undergoing NIPT testing with a single male fetus to demonstrate the influence of fetal fraction by the maternal and fetal characteristics. We show several fetal fraction discrepancies that contradict the generally presented conventional view. At first, the fetal fraction is not consistently rising with the maturity of the fetus due to a drop in 15 weeks of maturation. Secondly, the male samples have a lower fetal fraction than female fetuses, arguably due to the smaller gonosomal chromosomes. Finally, we discuss not only the possible reasons why this inconsistency exists but we also outline why these differences have not yet been identified and published. We demonstrate two non-intuitive trends to better comprehend the fetal fraction development and more precise selection of patients with sufficient fetal fraction for accurate testing. © 2022 The Authors},

keywords = {Genetic testing, Non-invasive prenatal testing, Prenatal diagnosis},

pubstate = {published},

tppubtype = {article}

}

@article{Rusňáková2022,

title = {Systematic Genomic Surveillance of SARS-CoV-2 Virus on Illumina Sequencing Platforms in the Slovak Republic—One Year Experience},

author = {D. Rusňáková and T. Sedláčková and P. Radvák and M. Böhmer and P. Mišenko and J. Budiš and S. Bokorová and N. Lipková and M. Forgáčová-Jakúbková and T. Sládeček and J. Sitarčík and W. Krampl and M. Gažiová and A. Kaliňáková and E. Staroňová and E. Tichá and T. Vrábľová and L. Ševčíková and B. Kotvasová and L. Maďarová and S. Feiková and K. Beňová and L. Reizigová and Z. Onderková and D. Ondrušková and D. Loderer and M. Škereňová and Z. Danková and K. Janíková and E. Halašová and E. Nováková and J. Turňa and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141590744&doi=10.3390%2fv14112432&partnerID=40&md5=ae8783f0d6a244a1eeea0fb3d17f7230},

doi = {10.3390/v14112432},

issn = {19994915},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Viruses},

volume = {14},

number = {11},

publisher = {MDPI},

abstract = {To explore a genomic pool of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the pandemic, the Ministry of Health of the Slovak Republic formed a genomics surveillance workgroup, and the Public Health Authority of the Slovak Republic launched a systematic national epidemiological surveillance using whole-genome sequencing (WGS). Six out of seven genomic centers implementing Illumina sequencing technology were involved in the national SARS-CoV-2 virus sequencing program. Here we analyze a total of 33,024 SARS-CoV-2 isolates collected from the Slovak population from 1 March 2021, to 31 March 2022, that were sequenced and analyzed in a consistent manner. Overall, 28,005 out of 30,793 successfully sequenced samples met the criteria to be deposited in the global GISAID database. During this period, we identified four variants of concern (VOC)—Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529). In detail, we observed 165 lineages in our dataset, with dominating Alpha, Delta and Omicron in three major consecutive incidence waves. This study aims to describe the results of a routine but high-level SARS-CoV-2 genomic surveillance program. Our study of SARS-CoV-2 genomes in collaboration with the Public Health Authority of the Slovak Republic also helped to inform the public about the epidemiological situation during the pandemic. © 2022 by the authors.},

keywords = {Sars-cov-2, Viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Smoľak2022,

title = {Analysis of RNA virome in rectal swabs of healthy and diarrheic pigs of different age},

author = {D. Smoľak and S. Šalamúnová and A. Jacková and M. Haršányová and J. Budiš and T. Szemes and Š. Vilček},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85140085232&doi=10.1016%2fj.cimid.2022.101892&partnerID=40&md5=e964d61275f2138aec68eafa8217a8a2},

doi = {10.1016/j.cimid.2022.101892},

issn = {01479571},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Comparative Immunology, Microbiology and Infectious Diseases},

volume = {90-91},

publisher = {Elsevier Ltd},

abstract = {The porcine enteric virome comprises a wide range of eukaryotic and prokaryotic viruses in healthy and diarrheic pigs. As RNA viruses are considered to be important agents responsible for diarrhoea in pigs, this work was focused on the RNA virome. To identify viruses, a next generation sequencing technique and bioinformatics analysis was employed. A wide spectrum of viral genera with RNA genomes, such as Kobuvirus, Picobirnavirus, Teschovirus, Posavirus, Mamastovirus, Enterovirus and Rotavirus were identified in both diarrheic and healthy pigs. No clear differences in the virome composition were found between healthy and diarrheic pigs. The data visualisation using Non-Metric Multidimensional Scaling as well as by the Analysis of Similarities test suggested that the virome depended on the age of animals and differed in piglets when compared to weaned and fattening pigs. © 2022 The Authors},

keywords = {Viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Eva2022568,

title = {Molecularly confi rmed pontocerebellar hypoplasia in a large family from Slovakia with four severely affected children},

author = {R. Eva and P. Zuzana and Z. Andrea and H. Michaela and B. Frantisek and S. Tomas and K. Ludevit and R. Jan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85134720652&doi=10.4149%2fBLL_2022_090&partnerID=40&md5=0d3c4a8ef35cc20d1dcb78f936fbc298},

doi = {10.4149/BLL_2022_090},

issn = {00069248},

year  = {2022},

date = {2022-01-01},

journal = {Bratislava Medical Journal},

volume = {123},

number = {8},

pages = {568-572},

publisher = {Comenius University in Bratislava},

abstract = {BACKGROUND: Pontocerebellar hypoplasia type 1 (PCH1) is characterized by a central and peripheral motor dysfunction associated with anterior horn cell degeneration, similar to spinal muscular atrophy (SMA). OBJECTIVES: We analysed three probands (later discovered to be siblings) suspected to have severe SMA, however, not confi rmed by genetic test. METHODS: Clinical-exome analysis (Illumina) was performed to identify causative variants, followed by Sanger sequencing confi rmation in probands and other 10 family members. RESULTS: Homozygous pathogenic variant c.92G>C (p.(Gly31Ala)) in the Exosome Component 3 (EXOSC3) gene was found in all 3 probands, thus confi rming the diagnosis of a severe form of PCH1B. The parents and six siblings were carriers, while one sibling was homozygous for a reference allele. This variant is frequent in the Czech Roma population, where it is considered a founder mutation. Haplotype analysis in this largest reported PCH1B family showed that our patients inherited from their father (of Roma origin) a haplotype identical to that found in the Czech Roma population, thus indicating these alleles have a common origin. CONCLUSION: This EXOSC3 variant is rare among the general population but most likely frequent also among Roma people in Slovakia. PCH1B should be considered for a differential diagnosis in infants manifesting SMA-like phenotype, especially if of Roma origin (Tab. 1, Fig. 1, Ref. 22). Text in PDF www.elis.sk © 2022. Bratislava Medical Journal.All Rights Reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hyblova2022,

title = {Maternal Copy Number Imbalances in Non-Invasive Prenatal Testing: Do They Matter?},

author = {M. Hyblova and A. Gnip and M. Kucharik and J. Budis and M. Sekelska and G. Minarik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85144618980&doi=10.3390%2fdiagnostics12123056&partnerID=40&md5=3f313608e34c3a2137159e1e157d014c},

doi = {10.3390/diagnostics12123056},

issn = {20754418},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Diagnostics},

volume = {12},

number = {12},

publisher = {MDPI},

abstract = {Non-invasive prenatal testing (NIPT) has become a routine practice in screening for common aneuploidies of chromosomes 21, 18, and 13 and gonosomes X and Y in fetuses worldwide since 2015 and has even expanded to include smaller subchromosomal events. In fact, the fetal fraction represents only a small proportion of cell-free DNA on a predominant background of maternal DNA. Unlike fetal findings that have to be confirmed using invasive testing, it has been well documented that NIPT provides information on maternal mosaicism, occult malignancies, and hidden health conditions due to copy number variations (CNVs) with diagnostic resolution. Although large duplications or deletions associated with certain medical conditions or syndromes are usually well recognized and easy to interpret, very little is known about small, relatively common copy number variations on the order of a few hundred kilobases and their potential impact on human health. We analyzed data from 6422 NIPT patient samples with a CNV detection resolution of 200 kb for the maternal genome and identified 942 distinct CNVs; 328 occurred repeatedly. We defined them as multiple occurring variants (MOVs). We scrutinized the most common ones, compared them with frequencies in the gnomAD SVs v2.1, dbVar, and DGV population databases, and analyzed them with an emphasis on genomic content and potential association with specific phenotypes. © 2022 by the authors.},

keywords = {Copy number variation, Non-invasive prenatal testing},

pubstate = {published},

tppubtype = {article}

}

@article{Soltész2022b,

title = {Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients},

author = {B. Soltész and O. Pös and Z. Wlachovska and J. Budis and R. Hekel and L. Strieskova and J. B. Liptak and W. Krampl and J. Styk and N. Németh and J. S. Keserű and A. Jenei and G. Buglyó and Á. Klekner and B. Nagy and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142723801&doi=10.1016%2fj.mcp.2022.101875&partnerID=40&md5=cfe8239029a20ab89e08e1321a98c75e},

doi = {10.1016/j.mcp.2022.101875},

issn = {08908508},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Molecular and Cellular Probes},

volume = {66},

publisher = {Academic Press},

abstract = {Glioblastoma is the most common malignant tumor of the central nervous system (CNS) in adults. Glioblastoma cells show increased glucose consumption associated with poor prognosis. Since mitochondria play a crucial role in energy metabolism, mutations and copy number changes of mitochondrial DNA may serve as biomarkers. As the brain is difficult to access, analysis of mitochondria directly from the brain tissue represents a challenge. Exosome analysis is an alternative (still poorly explored) approach to investigate molecular changes in CNS tumors. We analyzed brain tissue DNA and plasma-derived exosomal DNA (exoDNA) of 44 glioblastoma patients and 40 control individuals. Quantitative real-time PCR was performed to determine mtDNA copy numbers and the Kruskal-Wallis and Mann-Whitney U test were used for statistical analysis of data. Subsequently, sequencing libraries were prepared and sequenced on the MiSeq platform to identify mtDNA point mutations. Tissue mtDNA copy number was different among controls and patients in multiple comparisons. A similar tendency was detected in exosomes. Based on NGS analysis, several mtDNA point mutations showed slightly different frequencies between cases and controls, but the clinical relevance of these observations is difficult to assess and likely less than that of overall mtDNA copy number changes. Allele frequencies of variants were used to determine the level of heteroplasmy (found to be higher in exo-mtDNA of control individuals). Despite the suggested potential, the use of such biomarkers for the screening and/or diagnosis of glioblastomas is still limited, thus further studies are needed. © 2022},

keywords = {Copy number variation, Mitochondria, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Misova20211914,

title = {Repression of a large number of genes requires interplay between homologous recombination and HIRA},

author = {I Misova and A Pitelova and J Budis and J Gazdarica and T Sedlackova and A Jordakova and Z Benko and M Smondrkova and N Mayerova and K Pichlerova and L Strieskova and M Prevorovsky and J Gregan and L Cipak and T Szemes and S B Polakova},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85102408904&doi=10.1093%2fnar%2fgkab027&partnerID=40&md5=77d6eafd60e9cb1a1c3c8237566b8cc1},

doi = {10.1093/nar/gkab027},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {4},

pages = {1914-1934},

publisher = {Oxford University Press},

abstract = {During homologous recombination, Dbl2 protein is required for localisation of Fbh1, an F-box helicase that efficiently dismantles Rad51-DNA filaments. RNA-seq analysis of dbl2Δtranscriptome showed that the dbl2 deletion results in upregulation of more than 500 loci in Schizosaccharomyces pombe. Compared with the loci with no change in expression, the misregulated loci in dbl2Δare closer to long terminal and long tandem repeats. Furthermore, the misregulated loci overlap with antisense transcripts, retrotransposons, meiotic genes and genes located in subtelomeric regions. A comparison of the expression profiles revealed that Dbl2 represses the same type of genes as the HIRA histone chaperone complex. Although dbl2 deletion does not alleviate centromeric or telomeric silencing, it suppresses the silencing defect at the outer centromere caused by deletion of hip1 and slm9 genes encoding subunits of the HIRA complex. Moreover, our analyses revealed that cells lacking dbl2 show a slight increase of nucleosomes at transcription start sites and increased levels of methylated histone H3 (H3K9me2) at centromeres, subtelomeres, rDNA regions and long terminal repeats. Finally, we show that other proteins involved in homologous recombination, such as Fbh1, Rad51, Mus81 and Rad54, participate in the same gene repression pathway. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.},

keywords = {Epigenetics, Transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Ženišová202187,

title = {Effects of co-fermentation with lachancea thermotolerans or metschnikowia pulcherrima on concentration of aroma compounds in pinot blanc wine},

author = {K Ženišová and T Cabicarová and R Sidari and E Kolek and D Pangallo and T Szemes and T Kuchta},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85103857742&partnerID=40&md5=d4693544a7b1a478503ed67094155402},

issn = {13368672},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Food and Nutrition Research},

volume = {60},

number = {1},

pages = {87-91},

publisher = {Food Reseach Institute},

abstract = {Slovakian strains of Lachancea thermotolerans and Metschnikowia pulcherrima were used in sequential co-fermentation with Saccharomyces cerevisiae in small-scale production of Pinot Blanc wine from the Small Carpathian wine region in Slovakia. Aroma compounds of the produced wines were analysed using solid-phase microextraction coupled to gas chromatography-mass spectrometry. Thirty-six aroma compounds were quantified, demonstrating no significant differences in concentrations of almost half of them, including acetic acid, ethyl acetate, 2,3-butanediol and butanoic acid. Wines produced with non-Saccharomyces yeasts did not contain increased concentrations of aroma-active esters, but contained increased concentrations of methionol and decreased concentrations of furfural. Wine produced with L. thermotolerans contained increased concentrations of 2-phenylethanol, diethyl succinate and phenylethyl acetate, together with an increased concentration of 3-methylbutanoic acid. Wine produced with M. pulcherrima contained increased concentrations of 2-phenylethanol and diethyl succinate, together with a decreased concentration of acet-aldehyde. Results of the study demonstrate that L. thermotolerans and M. pulcherrima, when used in a co-culture with S. cerevisiae, can modulate the composition of Pinot Blanc wine regarding aroma compounds, thereby positively con-tributing to its quality. © 2021 National Agricultural and Food Centre (Slovakia).},

keywords = {Bacteria, Food microbiome, Fungi},

pubstate = {published},

tppubtype = {article}

}

@article{BágeľováPoláková2021,

title = {Mitochondrial DNA duplication, recombination, and introgression during interspecific hybridization},

author = {S Bágeľová Poláková and Ž Lichtner and T Szemes and M Smolejová and P Sulo},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85108161297&doi=10.1038%2fs41598-021-92125-y&partnerID=40&md5=6bc31d15f4fb89003df9c7623ab3db19},

doi = {10.1038/s41598-021-92125-y},

issn = {20452322},

year  = {2021},

date = {2021-01-01},

journal = {Scientific Reports},

volume = {11},

number = {1},

publisher = {Nature Research},

abstract = {mtDNA recombination events in yeasts are known, but altered mitochondrial genomes were not completed. Therefore, we analyzed recombined mtDNAs in six Saccharomyces cerevisiae × Saccharomyces paradoxus hybrids in detail. Assembled molecules contain mostly segments with variable length introgressed to other mtDNA. All recombination sites are in the vicinity of the mobile elements, introns in cox1, cob genes and free standing ORF1, ORF4. The transplaced regions involve co-converted proximal exon regions. Thus, these selfish elements are beneficial to the host if the mother molecule is challenged with another molecule for transmission to the progeny. They trigger mtDNA recombination ensuring the transfer of adjacent regions, into the progeny of recombinant molecules. The recombination of the large segments may result in mitotically stable duplication of several genes. © 2021, The Author(s).},

keywords = {Fungi, Mitochondria},

pubstate = {published},

tppubtype = {article}

}

@article{Kucharík2021,

title = {Copy number variant detection with low-coverage whole-genome sequencing represents a viable alternative to the conventional array-cgh},

author = {M Kucharík and J Budiš and M Hýblová and G Minárik and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109087040&doi=10.3390%2fdiagnostics11040708&partnerID=40&md5=6fdfa35027032bf889399d967bb1cce9},

doi = {10.3390/diagnostics11040708},

issn = {20754418},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Diagnostics},

volume = {11},

number = {4},

publisher = {MDPI AG},

abstract = {Copy number variations (CNVs) represent a type of structural variant involving alterations in the number of copies of specific regions of DNA that can either be deleted or duplicated. CNVs contribute substantially to normal population variability, however, abnormal CNVs cause numerous genetic disorders. At present, several methods for CNV detection are applied, ranging from the conventional cytogenetic analysis, through microarray-based methods (aCGH), to next-generation sequencing (NGS). In this paper, we present GenomeScreen, an NGS-based CNV detection method for low-coverage, whole-genome sequencing. We determined the theoretical limits of its accuracy and obtained confirmation in an extensive in silico study and in real patient samples with known genotypes. In theory, at least 6 M uniquely mapped reads are required to detect a CNV with the length of 100 kilobases (kb) or more with high confidence (Z-score > 7). In practice, the in silico analysis required at least 8 M to obtain >99% accuracy (for 100 kb deviations). We compared GenomeScreen with one of the currently used aCGH methods in diagnostic laboratories, which has mean resolution of 200 kb. GenomeScreen and aCGH both detected 59 deviations, while GenomeScreen furthermore detected 134 other (usually) smaller variations. When compared to aCGH, overall performance of the proposed GenemoScreen tool is comparable or superior in terms of accuracy, turn-around time, and cost-effectiveness, thus providing reasonable benefits, particularly in a prenatal diagnosis setting. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Cell-free nucleic acids, Computational method, Copy number variation, Liquid biopsy, Non-invasive prenatal testing},

pubstate = {published},

tppubtype = {article}

}

@article{Pecimonova2021e26136,

title = {Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report},

author = {M Pecimonova and J Radvanszky and D Smolak and J Budis and M Lichvar and D Kristinova and I Rozova and J Turna and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107796467&doi=10.1097%2fMD.0000000000026136&partnerID=40&md5=6d8eac607b0de5b1897c2cee34a64ec9},

doi = {10.1097/MD.0000000000026136},

issn = {15365964},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Medicine},

volume = {100},

number = {22},

pages = {e26136},

publisher = {NLM (Medline)},

abstract = {RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. DIAGNOSES: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. INTERVENTIONS AND OUTCOMES: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. LESSONS: We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available. Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.},

keywords = {Case study, Genetic testing, Single nucleotide variants, Variant interpretation},

pubstate = {published},

tppubtype = {article}

}

@article{Radvanszky2021,

title = {Characterisation of non-pathogenic premutation-range myotonic dystrophy type 2 alleles},

author = {J Radvanszky and M Hyblova and E Radvanska and P Spalek and A Valachova and G Magyarova and C Bognar and E Polak and T Szemes and L Kadasi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114043590&doi=10.3390%2fjcm10173934&partnerID=40&md5=57bc1cfc4be446edf6fbfea3c9ad284a},

doi = {10.3390/jcm10173934},

issn = {20770383},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Journal of Clinical Medicine},

volume = {10},

number = {17},

publisher = {MDPI},

abstract = {Myotonic dystrophy type 2 (DM2) is caused by expansion of a (CCTG)n repeat in the cellular retroviral nucleic acid-binding protein (CNBP) gene. The sequence of the repeat is most commonly interrupted and is stably inherited in the general population. Although expanded alleles, premutation range and, in rare cases, also non-disease associated alleles containing uninterrupted CCTG tracts have been described, the threshold between these categories is poorly characterised. Here, we describe four families with members reporting neuromuscular complaints, in whom we identified altogether nine ambiguous CNBP alleles containing uninterrupted CCTG repeats in the range between 32 and 42 repeats. While these grey-zone alleles are most likely not pathogenic themselves, since other pathogenic mutations were identified and particular family structures did not support their pathogenic role, they were found to be unstable during intergenerational transmission. On the other hand, there was no observable general microsatellite instability in the genome of the carriers of these alleles. Our results further refine the division of CNBP CCTG repeat alleles into two major groups, i.e., interrupted and uninterrupted alleles. Both interrupted and uninterrupted alleles with up to approximately 30 CCTG repeats were shown to be generally stable during intergenerational transmission, while intergenerational as well as somatic instability seems to gradually increase in uninterrupted alleles with tract length growing above this threshold. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Non-invasive prenatal testing, Oncology, Single nucleotide variants},

pubstate = {published},

tppubtype = {article}

}

@article{Forgacova2021,

title = {Repurposing non‑invasive prenatal testing data: Population study of single nucleotide variants associated with Colorectal Cancer and Lynch Syndrome},

author = {N Forgacova and J Gazdarica and J Budis and J Radvanszky and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85115197955&doi=10.3892%2fol.2021.13040&partnerID=40&md5=2e80f1d2538655ce09382de2cd0b3e20},

doi = {10.3892/ol.2021.13040},

issn = {17921074},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Oncology Letters},

volume = {22},

number = {5},

publisher = {Spandidos Publications},

abstract = {In our previous work, genomic data generated through non‑invasive prenatal testing (NIPT) based on low‑coverage massively parallel whole‑genome sequencing of totalplasmaDNAofpregnantwomeninSlovakiawasdescribed as a valuable source of population specific data. In the present study, these data were used to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, variants were interpreted, functional consequences were searched for and clinical significance of variants was investigated using publicly available databases. Although the present study did not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, significant differences were observed in the allelic frequency of risk CRC variants previously reported in genome‑wide association studies and common variants located in genes associated with LS. As Slovakia is one of the leading countries with the highest incidence of CRC among male patients in the world, there is a need for studies dedicated to investigating the cause of such a high incidence of CRC in Slovakia. The present study also assumed that extensive cross‑country data aggregation of NIPT results would represent an unprecedented source of information concerning human genome variation in cancer research. © 2021 Spandidos Publications. All rights reserved.},

keywords = {Non-invasive prenatal testing, Oncology, Population study},

pubstate = {published},

tppubtype = {article}

}

@article{Hekel2021,

title = {Privacy-preserving storage of sequenced genomic data},

author = {R. Hekel and J. Budis and M. Kucharik and J. Radvanszky and Z. Pös and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85116340115&doi=10.1186%2fs12864-021-07996-2&partnerID=40&md5=d65889f16bf2c9525f7bf6a7c6d8a129},

doi = {10.1186/s12864-021-07996-2},

issn = {14712164},

year  = {2021},

date = {2021-01-01},

journal = {BMC Genomics},

volume = {22},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: The current and future applications of genomic data may raise ethical and privacy concerns. Processing and storing of this data introduce a risk of abuse by potential offenders since the human genome contains sensitive personal information. For this reason, we have developed a privacy-preserving method, named Varlock providing secure storage of sequenced genomic data. We used a public set of population allele frequencies to mask the personal alleles detected in genomic reads. Each personal allele described by the public set is masked by a randomly selected population allele with respect to its frequency. Masked alleles are preserved in an encrypted confidential file that can be shared in whole or in part using public-key cryptography. Results: Our method masked the personal variants and introduced new variants detected in a personal masked genome. Alternative alleles with lower population frequency were masked and introduced more often. We performed a joint PCA analysis of personal and masked VCFs, showing that the VCFs between the two groups cannot be trivially mapped. Moreover, the method is reversible and personal alleles in specific genomic regions can be unmasked on demand. Conclusion: Our method masks personal alleles within genomic reads while preserving valuable non-sensitive properties of sequenced DNA fragments for further research. Personal alleles in the desired genomic regions may be restored and shared with patients, clinics, and researchers. We suggest that the method can provide an additional security layer for storing and sharing of the raw aligned reads. © 2021, The Author(s).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pös20211,

title = {Copy number variation: Methods and clinical applications},

author = {O Pös and J Radvanszky and J Styk and Z Pös and G Buglyó and M Kajsik and J Budis and B Nagy and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099826325&doi=10.3390%2fapp11020819&partnerID=40&md5=bf6fb8a1dd856194a109626d3ad1f9ca},

doi = {10.3390/app11020819},

issn = {20763417},

year  = {2021},

date = {2021-01-01},

journal = {Applied Sciences (Switzerland)},

volume = {11},

number = {2},

pages = {1-16},

publisher = {MDPI AG},

abstract = {Gains and losses of large segments of genomic DNA, known as copy number variants (CNVs) gained considerable interest in clinical diagnostics lately, as particular forms may lead to inherited genetic diseases. In recent decades, researchers developed a wide variety of cytogenetic and molecular methods with different detection capabilities to detect clinically relevant CNVs. In this review, we summarize methodological progress from conventional approaches to current state of the art techniques capable of detecting CNVs from a few bases up to several megabases. Although the recent rapid progress of sequencing methods has enabled precise detection of CNVs, determining their functional effect on cellular and whole-body physiology remains a challenge. Here, we provide a comprehensive list of databases and bioinformatics tools that may serve as useful assets for researchers, laboratory diagnosticians, and clinical geneticists facing the challenge of CNV detection and interpretation. © 2021 by the authors.},

keywords = {Copy number variation, Review, Variant interpretation},

pubstate = {published},

tppubtype = {article}

}

@article{Maronek2021,

title = {Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice},

author = {M Maronek and B Gromova and R Liptak and B Konecna and M Pastorek and B Cechova and M Harsanyova and J Budis and D Smolak and J Radvanszky and T Szemes and J Harsanyiova and A Kralova Trancikova and R Gardlik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099721641&doi=10.3390%2fcells10010081&partnerID=40&md5=e2a2d57bcd02c36a1091367862022bb1},

doi = {10.3390/cells10010081},

issn = {20734409},

year  = {2021},

date = {2021-01-01},

journal = {Cells},

volume = {10},

number = {1},

publisher = {NLM (Medline)},

abstract = {Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.},

keywords = {Body fluids, Cell-free nucleic acids},

pubstate = {published},

tppubtype = {article}

}

@article{Böhmer2020b,

title = {Comparison of microbial diversity during two different wine fermentation processes},

author = {M Böhmer and D Smoľak and K Ženišová and Z Čaplová and D Pangallo and A Puškárová and M Bučková and T Cabicarová and J Budiš and K Šoltýs and D Rusňáková and T Kuchta and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091808679&doi=10.1093%2ffemsle%2ffnaa150&partnerID=40&md5=bc04ad6a27036f5f7562c73abecb183f},

doi = {10.1093/femsle/fnaa150},

issn = {15746968},

year  = {2020},

date = {2020-01-01},

journal = {FEMS microbiology letters},

volume = {367},

number = {18},

publisher = {NLM (Medline)},

abstract = {Wine production is a complex procedure in which an important role is played by many microorganisms, particularly yeasts and bacteria. In modern wineries, alcoholic fermentation is usually carried out by adding microbial starter cultures of Saccharomyces cerevisiae strains for precisely controlled production. Nowadays, in the Slovak Republic, autochthonous vinification is getting more popular. The present article deals with the comparison of two vinification approaches, namely spontaneous fermentation and fermentation controlled by a standard commercial S. cerevisiae starter, from the point of view of microbiota dynamics and the chemical characteristics of the wines produced. The dynamics of microbial populations were determined during the fermentation process by a 16S and 28S rRNA next-generation sequencing approach. A profile of the volatile compounds during these fermentation processes was identified by solid-phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS). In summary, the microbial diversity in the m1 phase (initial must) was higher, despite the presence of the starter culture. In the m3 phase (young wine), the microbiome profiles of both batches were very similar. It seems that the crucial phase in order to study the relationship of the microbiome and the resulting product should be based on the m2 phase (fermented must), where the differences between the autochthonous and inoculated batches were more evident. © The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.},

keywords = {Bacteria, Food microbiome, Fungi, Metagenomics, Plants},

pubstate = {published},

tppubtype = {article}

}

@article{Böhmer20201,

title = {Identification of bacterial and fungal communities in the roots of orchids and surrounding soil in heavy metal contaminated area of mining heaps},

author = {M Böhmer and D Ozdín and M Račko and M Lichvár and J Budiš and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85093967272&doi=10.3390%2fapp10207367&partnerID=40&md5=a65386928d7c2f6f118d18ce7a0e4bb3},

doi = {10.3390/app10207367},

issn = {20763417},

year  = {2020},

date = {2020-01-01},

journal = {Applied Sciences (Switzerland)},

volume = {10},

number = {20},

pages = {1-18},

publisher = {MDPI AG},

abstract = {Orchids represent a unique group of plants that are well adapted to extreme conditions. In our study, we aimed to determine if different soil contamination and pH significantly change fungal and bacterial composition. We identified bacterial and fungal communities from the roots and the surrounding soil of the family Orchidaceae growing on different mining sites in Slovakia. These communities were detected from the samples of Cephalanthera longifolia and Epipactis pontica from Fe deposit Sirk, E. atrorubens from Ni-Co deposit Dobšiná and Pb-Zn deposit Jasenie and Platanthera bifolia by 16S rRNA gene and ITS next-generation sequencing method. A total of 171 species of fungi and 30 species of bacteria were detected from five samples of orchids. In summary, slight differences in pH of the initial soils do not significantly affect the presence of fungi and bacteria and thus the presence of the studied orchids in these localities. Similarly, the toxic elements in the studied localities, do not affect the occurrence of fungi, bacteria, and orchids. Moreover, Cortinarius saturatus, as a dominant fungus, and Candidatus Udaeobacter as a dominant bacterium were present in all soil samples and some root samples. Finally, many of these fungal and bacterial communities have the potential to be used in the bioremediation of the mining areas. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},

keywords = {Bacteria, Environmental microbiome, Metagenomics, Plants},

pubstate = {published},

tppubtype = {article}

}

@article{Hyblova2020,

title = {Validation of copy number variants detection from pregnant plasma using low-pass whole-genome sequencing in noninvasive prenatal testing-like settings},

author = {M Hyblova and M Harsanyova and D Nikulenkov-Grochova and J Kadlecova and M Kucharik and J Budis and G Minarik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090251668&doi=10.3390%2fdiagnostics10080569&partnerID=40&md5=b34f5ed83d4c332d97149be1644573c0},

doi = {10.3390/diagnostics10080569},

issn = {20754418},

year  = {2020},

date = {2020-01-01},

journal = {Diagnostics},

volume = {10},

number = {8},

publisher = {MDPI AG},

abstract = {Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).},

keywords = {Copy number variation, Fetal fraction, Non-invasive prenatal testing, Validation},

pubstate = {published},

tppubtype = {article}

}

@article{Kucharik2020,

title = {Non-invasive prenatal testing (NIPT) by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions},

author = {M Kucharik and A Gnip and M Hyblova and J Budis and L Strieskova and M Harsanyova and O Pös and Z Kubiritova and J Radvanszky and G Minarik and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089990305&doi=10.1371%2fjournal.pone.0238245&partnerID=40&md5=56850bc0c9e9e5e266a3538da3dd5bed},

doi = {10.1371/journal.pone.0238245},

issn = {19326203},

year  = {2020},

date = {2020-01-01},

journal = {PLoS ONE},

volume = {15},

number = {8 August},

publisher = {Public Library of Science},

abstract = {To study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes. We used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts. The in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples. Our results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening/diagnostics procedure, however, accuracy and reliability depends on several specific factors. Copyright: © 2020 Kucharik et al.},

keywords = {Copy number variation, Fetal fraction, Non-invasive prenatal testing, Validation},

pubstate = {published},

tppubtype = {article}

}