Spolupracovali sme na publikáciach
2022
4.
Gažiová, M.; Sládeček, T.; Pös, O.; Števko, M.; Krampl, W.; Pös, Z.; Hekel, R.; Hlavačka, M.; Kucharík, M.; Radvánszky, J.; Budiš, J.; Szemes, T.
Automated prediction of the clinical impact of structural copy number variations Journal Article
V: Scientific Reports, 12 (1), 2022, ISSN: 20452322.
Abstrakt | Linky | BibTeX | Značky: Computational method, Copy number variation, Variant interpretation
@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}
}
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).
2021
3.
Pös, O; Radvanszky, J; Styk, J; Pös, Z; Buglyó, G; Kajsik, M; Budis, J; Nagy, B; Szemes, T
Copy number variation: Methods and clinical applications Journal Article
V: Applied Sciences (Switzerland), 11 (2), pp. 1-16, 2021, ISSN: 20763417.
Abstrakt | Linky | BibTeX | Značky: Copy number variation, Review, Variant interpretation
@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}
}
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.
2.
Pecimonova, M; Radvanszky, J; Smolak, D; Budis, J; Lichvar, M; Kristinova, D; Rozova, I; Turna, J; Szemes, T
Admixed phenotype of NEDD4L associated periventricular nodular heterotopia: A case report Journal Article
V: Medicine, 100 (22), pp. e26136, 2021, ISSN: 15365964.
Abstrakt | Linky | BibTeX | Značky: Case study, Genetic testing, Single nucleotide variants, Variant interpretation
@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}
}
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.
2015
1.
Radvánszky, J; Minárik, G; Szemeš, T; Konečný, M; Kádaši, L
V: Lekarsky Obzor, 64 (11), pp. 418-427, 2015, ISSN: 04574214.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Review, Single nucleotide variants, Variant interpretation
@article{Radvánszky2015418,
title = {Interpretation of clinical significance of sequence variants in molecular genetics [Interpretácia klinického významu sekvenčných variantov v molekulovej genetike]},
author = {J Radvánszky and G Minárik and T Szemeš and M Konečný and L Kádaši},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020271195&partnerID=40&md5=bf647ff52f306470833ee835a42d012b},
issn = {04574214},
year = {2015},
date = {2015-01-01},
journal = {Lekarsky Obzor},
volume = {64},
number = {11},
pages = {418-427},
publisher = {Slovenska zdravotnicka univerzita},
abstract = {By applications of genomic analyses we are able to get an enormous number of different sequence variants in each analysed individual. From these only a small, although constantly growing, number of variants are already known and well characterised, while the majority of them are yet not characterised unknown variants. Their correct classification and interpretation are key factors for the understanding and usage of their informational value in clinical practice. Consistent education of professional staff able to handle, interpret and transfer the generated data to clinical workflow represents therefore a very important factor of professional practice. This article summarizes different recommendations for the evaluation and interpretation of sequence variants, from their correct nomenclature up to assigning them certain clinically relevant significance.},
keywords = {Genetic testing, Review, Single nucleotide variants, Variant interpretation},
pubstate = {published},
tppubtype = {article}
}
By applications of genomic analyses we are able to get an enormous number of different sequence variants in each analysed individual. From these only a small, although constantly growing, number of variants are already known and well characterised, while the majority of them are yet not characterised unknown variants. Their correct classification and interpretation are key factors for the understanding and usage of their informational value in clinical practice. Consistent education of professional staff able to handle, interpret and transfer the generated data to clinical workflow represents therefore a very important factor of professional practice. This article summarizes different recommendations for the evaluation and interpretation of sequence variants, from their correct nomenclature up to assigning them certain clinically relevant significance.