Publikácie

@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{Kubiritova201964,

title = {On the critical evaluation and confirmation of germline sequence variants identified using massively parallel sequencing},

author = {Z Kubiritova and M Gyuraszova and E Nagyova and M Hyblova and M Harsanyova and J Budis and R Hekel and J Gazdarica and F Duris and L Kadasi and T Szemes and J Radvanszky},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064435175&doi=10.1016%2fj.jbiotec.2019.04.013&partnerID=40&md5=175358cc48df08933da3da830780ad66},

doi = {10.1016/j.jbiotec.2019.04.013},

issn = {01681656},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Biotechnology},

volume = {298},

pages = {64-75},

publisher = {Elsevier B.V.},

abstract = {Although massively parallel sequencing (MPS) is becoming common practice in both research and routine clinical care, confirmation requirements of identified DNA variants using alternative methods are still topics of debate. When evaluating variants directly from MPS data, different read depth statistics, together with specialized genotype quality scores are, therefore, of high relevance. Here we report results of our validation study performed in two different ways: 1) confirmation of MPS identified variants using Sanger sequencing; and 2) simultaneous Sanger and MPS analysis of exons of selected genes. Detailed examination of false-positive and false-negative findings revealed typical error sources connected to low read depth/coverage, incomplete reference genome, indel realignment problems, as well as microsatellite associated amplification errors leading to base miss-calling. However, all these error types were identifiable with thorough manual revision of aligned reads according to specific patterns of distributions of variants and their corresponding reads. Moreover, our results point to dependence of both basic quantitative metrics (such as total read counts, alternative allele read counts and allelic balance) together with specific genotype quality scores on the used bioinformatics pipeline, stressing thus the need for establishing of specific thresholds for these metrics in each laboratory and for each involved pipeline independently. © 2019 Elsevier B.V.},

keywords = {Genetic testing, Single nucleotide variants, Validation, Variant calling},

pubstate = {published},

tppubtype = {article}

}

@article{Budiš20191310,

title = {Dante: Genotyping of known complex and expanded short tandem repeats},

author = {J Budiš and M Kucharík and F Duriš and J Gazdarica and M Zrubcová and A Ficek and T Szemes and B Brejová and J Radvanszky},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064435619&doi=10.1093%2fbioinformatics%2fbty791&partnerID=40&md5=7e873f64aff7726aeb724a3a0c37237f},

doi = {10.1093/bioinformatics/bty791},

issn = {13674803},

year  = {2019},

date = {2019-01-01},

journal = {Bioinformatics},

volume = {35},

number = {8},

pages = {1310-1317},

publisher = {Oxford University Press},

abstract = {Motivation: Short tandem repeats (STRs) are stretches of repetitive DNA in which short sequences, typically made of 2-6 nucleotides, are repeated several times. Since STRs have many important biological roles and also belong to the most polymorphic parts of the human genome, they became utilized in several molecular-genetic applications. Precise genotyping of STR alleles, therefore, was of high relevance during the last decades. Despite this, massively parallel sequencing (MPS) still lacks the analysis methods to fully utilize the information value of STRs in genome scale assays. Results: We propose an alignment-free algorithm, called Dante, for genotyping and characterization of STR alleles at user-specified known loci based on sequence reads originating from STR loci of interest. The method accounts for natural deviations from the expected sequence, such as variation in the repeat count, sequencing errors, ambiguous bases and complex loci containing several different motifs. In addition, we implemented a correction for copy number defects caused by the polymerase induced stutter effect as well as a prediction of STR expansions that, according to the conventional view, cannot be fully captured by inherently short MPS reads. We tested Dante on simulated datasets and on datasets obtained by targeted sequencing of protein coding parts of thousands of selected clinically relevant genes. In both these datasets, Dante outperformed HipSTR and GATK genotyping tools. Furthermore, Dante was able to predict allele expansions in all tested clinical cases. Availability and implementation: Dante is open source software, freely available for download at https://github.com/jbudis/dante. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.},

keywords = {Computational method, Genetic testing, Short tandem repeats, Variant calling},

pubstate = {published},

tppubtype = {article}

}

@article{Nagyova201946,

title = {Targeted next-generation sequencing in Slovak cardiomyopathy patients},

author = {E Nagyova and J Radvanszky and M Hyblova and V Simovicova and E Goncalvesova and F W Asselbergs and L Kadasi and T Szemes and G Minarik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060659545&doi=10.4149%2fBLL_2019_007&partnerID=40&md5=4242fb0c864e6c82fe2565c6cc094102},

doi = {10.4149/BLL_2019_007},

issn = {00069248},

year  = {2019},

date = {2019-01-01},

journal = {Bratislava Medical Journal},

volume = {120},

number = {1},

pages = {46-51},

publisher = {Comenius University},

abstract = {OBJECTIVES: For the first time we used targeted next-generation sequencing to detect candidate pathogenic variants in Slovak cardiomyopathy patients. BACKGROUND: Targeted next-generation sequencing is considered to be the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. METHODS: We used a panel of 46 known cardiomyopathy-associated genes to detect genetic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). RESULTS: We identified candidate pathogenic variants in 11 of 16 patients (69 %). Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Seven variants ACTC1 (c.329C > T), ANKRD1 (c.683G > T), MYH7 (c.1025C > T), PKP2 (c.2003delA), TTN (c.51655C > T, c.84841G > T, c.101874_101881delAGAATTTG) have been detected for the first time and might represent Slovak- specific genetic cause. CONCLUSIONS: We have performed genetic testing of previously untested Slovak cardiomyopathy patients using next-generation sequencing cardiomyopathy gene panel. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia. © AEPress s.r.o.},

keywords = {Genetic testing, Single nucleotide variants, Variant calling},

pubstate = {published},

tppubtype = {article}

}

@article{Radvanszky2017339,

title = {Complex phenotypes blur conventional borders between Say–Barber–Biesecker–Young–Simpson syndrome and genitopatellar syndrome},

author = {J Radvanszky and M Hyblova and D Durovcikova and M Hikkelova and E Fiedler and L Kadasi and J Turna and G Minarik and T Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84989325626&doi=10.1111%2fcge.12840&partnerID=40&md5=f3981a3dbb893dceec013f830ecf68f6},

doi = {10.1111/cge.12840},

issn = {00099163},

year  = {2017},

date = {2017-01-01},

journal = {Clinical Genetics},

volume = {91},

number = {2},

pages = {339-343},

publisher = {Blackwell Publishing Ltd},

abstract = {Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd},

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

pubstate = {published},

tppubtype = {article}

}