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.

Basic information

Original name

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

Authors

VALLOVÁ, Vladimíra (703 Slovakia, guarantor, belonging to the institution), Kristína HANDZUŠOVÁ (703 Slovakia, belonging to the institution), Markéta WAYHELOVÁ (203 Czech Republic, belonging to the institution), Petr BROŽ (203 Czech Republic, belonging to the institution), Aneta MIKULÁŠOVÁ (203 Czech Republic), Jan SMETANA (203 Czech Republic, belonging to the institution), Renata GAILLYOVÁ (203 Czech Republic, belonging to the institution) and Petr KUGLÍK (203 Czech Republic, belonging to the institution)

Edition

14th European Cytogenomics Conference, 2023

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10603 Genetics and heredity

Country of publisher

Austria

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14310/23:00131213

Organization unit

Faculty of Science

Keywords in English

exome sequencing; copy-number variations; neurodevelopmental disorders

Abstract

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.

Links

NU20-07-00145, research and development project

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

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Citovat

VALLOVÁ, Vladimíra, Kristína HANDZUŠOVÁ, Markéta WAYHELOVÁ, Petr BROŽ, Aneta MIKULÁŠOVÁ, Jan SMETANA, Renata GAILLYOVÁ and 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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