Different strategies for the detection of copy number
variations from exome sequencing data

a 2023

Different strategies for the detection of copy number variations from exome sequencing data

VALLOVÁ, Vladimíra, Kristína HANDZUŠOVÁ, Markéta WAYHELOVÁ, Petr BROŽ, Aneta MIKULÁŠOVÁ et. al.

Základní údaje

Originální název

Different strategies for the detection of copy number variations from exome sequencing data

Autoři

VALLOVÁ, Vladimíra (703 Slovensko, garant, domácí), Kristína HANDZUŠOVÁ (703 Slovensko, domácí), Markéta WAYHELOVÁ (203 Česká republika, domácí), Petr BROŽ (203 Česká republika, domácí), Aneta MIKULÁŠOVÁ (203 Česká republika), Jan SMETANA (203 Česká republika, domácí), Renata GAILLYOVÁ (203 Česká republika, domácí) a Petr KUGLÍK (203 Česká republika, domácí)

Vydání

14th European Cytogenomics Conference, 2023

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10603 Genetics and heredity

Stát vydavatele

Rakousko

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14310/23:00131213

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

exome sequencing; copy-number variations; neurodevelopmental disorders

Příznaky

Mezinárodní význam

Změněno: 12. 7. 2023 14:29, Mgr. Markéta Wayhelová, Ph.D.

Anotace

V originále

The development of special algorithms has recently brought copy-number variation (CNV) detection by exome sequencing (ES) much more to the forefront. There is no one-size-fits-all approach for reliable detection of CNVs from ES data. On the contrary, many different approaches combining capture kits and bioinformatics approaches are being tested for their detection. Total of fifteen samples with twenty rare CNVs (14,5 kb – 8 Mb) - using high-resolution chromosomal microarray analysis (CMA) as a standard - were selected for comparison of two different capture designs and five different read-depth based CNV calling strategies: Human Core Exome (HCE) from Twist Biosciences (CNVRobot (CNVR), in-house pipeline (IHP)) and SureSelect All Exon v7 (SSEL) from Agilent Technologies (Circular Binary Segmentation (CBS), Hidden Markov Model (HMM), ExomeDepth). Of the twenty rare CNVs tested, three strategies (CNVR and IHP for HCE and ExomeDepth for SSEL) were able to identify all of them. The CBS- and HMM-based strategies (SSEL) missed three and two CNVs, respectively. Differences were observed between the size of CNVs obtained by CMA and by the different ES CNV calling strategies. These differences arise from the different CMA probes and ES targets distributions along with the variable bioinformatics pipeline settings in the case of ES. In addition, ES CNV calling was able to detect intra-exonic rearrangements (in ZC4H2, GRIN2A, BRCA1, RNF125 genes), confirmed by qPCR. In summary, ES is a suitable approach for CNV detection. However, its reliability strongly depends on sequencing quality and data uniformity. In general, the combination of different CNV calling strategies can improve the reliability of CNV detection from ES data. Supported by Ministry of Health of the Czech Republic, grant nr. NU20-07-00145 and by Ministry of Health, Czech Republic - conceptual development of research organization (FNBr, 65269705). All rights reserved.

Návaznosti

NU20-07-00145, projekt VaV

Název: Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění

Investor: Ministerstvo zdravotnictví ČR, Úloha patogenních genetických variant detekovaných pomocí exomového sekvenování v etiologii dětských neurovývojových onemocnění, Podprogram 1 - standardní

Citovat

VALLOVÁ, Vladimíra, Kristína HANDZUŠOVÁ, Markéta WAYHELOVÁ, Petr BROŽ, Aneta MIKULÁŠOVÁ, Jan SMETANA, Renata GAILLYOVÁ a Petr KUGLÍK. Different strategies for the detection of copy number variations from exome sequencing data. In 14th European Cytogenomics Conference. 2023.

@proceedings{2297142,
   author = {Vallová, Vladimíra and Handzušová, Kristína and Wayhelová, Markéta and Brož, Petr and Mikulášová, Aneta and Smetana, Jan and Gaillyová, Renata and Kuglík, Petr},
   booktitle = {14th European Cytogenomics Conference},
   keywords = {exome sequencing; copy-number variations; neurodevelopmental disorders},
   language = {eng},
   title = {Different strategies for the detection of copy number variations from exome sequencing data},
   year = {2023}
}

TY  - CONF
ID  - 2297142
AU  - Vallová, Vladimíra - Handzušová, Kristína - Wayhelová, Markéta - Brož, Petr - Mikulášová, Aneta - Smetana, Jan - Gaillyová, Renata - Kuglík, Petr
PY  - 2023
TI  - Different strategies for the detection of copy number variations from exome sequencing data
KW  - exome sequencing
KW  - copy-number variations
KW  - neurodevelopmental disorders
N2  - The development of special algorithms has recently brought copy-number variation (CNV) detection by exome sequencing (ES) much more to the forefront. There is no one-size-fits-all approach for reliable detection of CNVs from ES data. On the contrary, many different approaches combining capture kits and bioinformatics approaches are being tested for their detection. Total of fifteen samples with twenty rare CNVs (14,5 kb – 8 Mb) - using high-resolution chromosomal microarray analysis (CMA) as a standard - were selected for comparison of two different capture designs and five different read-depth based CNV calling strategies: Human Core Exome (HCE) from Twist Biosciences (CNVRobot (CNVR), in-house pipeline (IHP)) and SureSelect All Exon v7 (SSEL) from Agilent Technologies (Circular Binary Segmentation (CBS), Hidden Markov Model (HMM), ExomeDepth). Of the twenty rare CNVs tested, three strategies (CNVR and IHP for HCE and ExomeDepth for SSEL) were able to identify all of them. The CBS- and HMM-based strategies (SSEL) missed three and two CNVs, respectively. Differences were observed between the size of CNVs obtained by CMA and by the different ES CNV calling strategies. These differences arise from the different CMA probes and ES targets distributions along with the variable bioinformatics pipeline settings in the case of ES. In addition, ES CNV calling was able to detect intra-exonic rearrangements (in ZC4H2, GRIN2A, BRCA1, RNF125 genes), confirmed by qPCR. In summary, ES is a suitable approach for CNV detection. However, its reliability strongly depends on sequencing quality and data uniformity. In general, the combination of different CNV calling strategies can improve the reliability of CNV detection from ES data. Supported by Ministry of Health of the Czech Republic, grant nr. NU20-07-00145 and by Ministry of Health, Czech Republic - conceptual development of research organization (FNBr, 65269705). All rights reserved.
ER  -

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