Publications

@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{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{Pös2019,

title = {Identification of structural variation from NGS-based non-invasive prenatal testing},

author = {O Pös and J Budis and Z Kubiritova and M Kucharik and F Duris and J Radvanszky and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071973486&doi=10.3390%2fijms20184403&partnerID=40&md5=2b201ce501881c47092d14454e2ed2a9},

doi = {10.3390/ijms20184403},

issn = {16616596},

year  = {2019},

date = {2019-01-01},

journal = {International Journal of Molecular Sciences},

volume = {20},

number = {18},

publisher = {MDPI AG},

abstract = {Copy number variants (CNVs) are an important type of human genome variation, which play a significant role in evolution contribute to population diversity and human genetic diseases. In recent years, next generation sequencing has become a valuable tool for clinical diagnostics and to provide sensitive and accurate approaches for detecting CNVs. In our previous work, we described a non-invasive prenatal test (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA for detection of CNV aberrations ≥600 kbp. We reanalyzed NIPT genomic data from 5018 patients to evaluate CNV aberrations in the Slovak population. Our analysis of autosomal chromosomes identified 225 maternal CNVs (47 deletions; 178 duplications) ranging from 600 to 7820 kbp. According to the ClinVar database, 137 CNVs (60.89%) were fully overlapping with previously annotated variants, 66 CNVs (29.33%) were in partial overlap, and 22 CNVs (9.78%) did not overlap with any previously described variant. Identified variants were further classified with the AnnotSV method. In summary, we identified 129 likely benign variants, 13 variants of uncertain significance, and 83 likely pathogenic variants. In this study, we use NIPT as a valuable source of population specific data. Our results suggest the utility of genomic data from commercial CNV analysis test as background for a population study. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.},

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

pubstate = {published},

tppubtype = {article}

}

@article{Budis201972,

title = {Non-invasive prenatal testing as a valuable source of population specific allelic frequencies},

author = {J Budis and J Gazdarica and J Radvanszky and M Harsanyova and I Gazdaricova and L Strieskova and R Frno and F Duris and G Minarik and M Sekelska and B Nagy and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064459936&doi=10.1016%2fj.jbiotec.2019.04.026&partnerID=40&md5=73c18a2081a2ec5ead08247b7543d15b},

doi = {10.1016/j.jbiotec.2019.04.026},

issn = {01681656},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Biotechnology},

volume = {299},

pages = {72-78},

publisher = {Elsevier B.V.},

abstract = {Low-coverage massively parallel genome sequencing for non-invasive prenatal testing (NIPT)of common aneuploidies is one of the most rapidly adopted and relatively low-cost DNA tests. Since aggregation of reads from a large number of samples allows overcoming the problems of extremely low coverage of individual samples, we describe the possible re-use of the data generated during NIPT testing for genome scale population specific frequency determination of small DNA variants, requiring no additional costs except of those for the NIPT test itself. We applied our method to a data set comprising of 1501 original NIPT test results and evaluated the findings on different levels, from in silico population frequency comparisons up to wet lab validation analyses using a gold-standard method based on Sanger sequencing. The revealed high reliability of variant calling and allelic frequency determinations suggest that these NIPT data could serve as valuable alternatives to large scale population studies even for smaller countries around the world. © 2019 Elsevier B.V.},

keywords = {Non-invasive prenatal testing, Population study, Single nucleotide variants, Variant calling},

pubstate = {published},

tppubtype = {article}

}

@article{Minárik2013539,

title = {Spectrum of mutations in gastrointestinal stromal tumor patients - a population-based study from Slovakia},

author = {G Minárik and L Plank and Z Lasabová and T Szemes and T Burjanivová and P Szépe and V Buzalková and D Porubský and J Šufliarsky},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878263424&doi=10.1111%2fapm.12019&partnerID=40&md5=dbaf848510fcae4f4e67f5505c875199},

doi = {10.1111/apm.12019},

issn = {09034641},

year  = {2013},

date = {2013-01-01},

journal = {APMIS},

volume = {121},

number = {6},

pages = {539-548},

abstract = {Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract and are characterized by presence of mutations in tyrosine kinases cKIT (KIT) and PDGFRα (PDGFRA). Mutations identified are highly heterogeneous, but some mutations are associated with specific clinical features of the tumor. Samples from 278 GIST patients collected during the period 2004-2011 were screened for mutations in exons 9, 11, 13, and 17 of KIT and 12, 14 and 18 of PDGFRA. Results of mutation screening were summarized and tested for possible association with clinical parameters of tumors. Mutations were identified in 83.81% of patients. Most frequent mutations were found in KIT exon 11 reaching frequency of 62.95%. Other exons contributed to the mutation pool with frequencies 8.27%, 7.55%, 2.52%, 1.44%, 1.08%, and 0.00%, in decreasing order KIT exon 9, PDGRFA exons 18 and 12, KIT exon 13, PDGFRA exon 14, and KIT exon 17. General linear model analysis showed no effect of any individual analyzed mutation on the phenotypic variables, but we confirmed association between mutations KIT exon 9 p. 503-504_dup2, and PDGFRA exon 18 p. D842V and intestinal and gastric localization of tumors. © 2012 APMIS.},

keywords = {Oncology, Population study, Single nucleotide variants},

pubstate = {published},

tppubtype = {article}

}