Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Burcu Yaldiz; Erdi Kucuk; Juliet Hampstead; Tom Hofste; Rolph Pfundt; Jordi Corominas Galbany; Tuula Rinne; Helger G. Yntema; Alexander Hoischen; Marcel Nelen; Christian Gilissen; Solve-RD consortium; Olaf Riess; Tobias B. Haack; Holm Graessner; Birte Zurek; Kornelia Ellwanger; Stephan Ossowski; German Demidov; Marc Sturm; Julia M. Schulze-Hentrich; Rebecca Schüle; Jishu Xu; Christoph Kessler; Melanie Wayand; Matthis Synofzik; Carlo Wilke; Andreas Traschütz; Ludger Schöls; Holger Hengel; Holger Lerche; Josua Kegele; Peter Heutink; Han Brunner; Hans Scheffer; Nicoline Hoogerbrugge; Alexander Hoischen; Peter A.C.’t Hoen; Lisenka E.L.M. Vissers; Christian Gilissen; Wouter Steyaert; Karolis Sablauskas; Richarda M. de Voer; Erik Jan Kamsteeg; Bart van de Warrenburg; Nienke van Os; Iris te Paske; Erik Janssen; Jill Clayton-Smith; Siddharth Banka; Adam Jackson; et al.

doi:10.1186/s40246-023-00485-5

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Burcu Yaldiz, Erdi Kucuk, Juliet Hampstead, Tom Hofste, Rolph Pfundt, Jordi Corominas Galbany, Tuula Rinne, Helger G. Yntema, Alexander Hoischen, Marcel Nelen, Christian Gilissen^*, Solve-RD consortium, Olaf Riess, Tobias B. Haack, Holm Graessner, Birte Zurek, Kornelia Ellwanger, Stephan Ossowski, German Demidov, Marc SturmJulia M. Schulze-Hentrich, Rebecca Schüle, Jishu Xu, Christoph Kessler, Melanie Wayand, Matthis Synofzik, Carlo Wilke, Andreas Traschütz, Ludger Schöls, Holger Hengel, Holger Lerche, Josua Kegele, Peter Heutink, Han Brunner, Hans Scheffer, Nicoline Hoogerbrugge, Alexander Hoischen, Peter A.C.’t Hoen, Lisenka E.L.M. Vissers, Christian Gilissen^*, Wouter Steyaert, Karolis Sablauskas, Richarda M. de Voer, Erik Jan Kamsteeg, Bart van de Warrenburg, Nienke van Os, Iris te Paske, Erik Janssen, Jill Clayton-Smith, Siddharth Banka, Adam Jackson, et al.

^*Corresponding author for this work

Division of Evolution, Infection and Genomics

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results: We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion: We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.

Original language	English
Article number	39
Journal	Human Genomics
Volume	17
Issue number	1
Early online date	3 May 2023
DOIs	https://doi.org/10.1186/s40246-023-00485-5
Publication status	Published - Dec 2023

Keywords

Exome sequencing
Genome sequencing
Uniformity of coverage
High-Throughput Nucleotide Sequencing/methods
Exome Sequencing
Humans
Genome, Human/genetics
Base Sequence
Exome/genetics
DNA Copy Number Variations/genetics

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Yaldiz, B., Kucuk, E., Hampstead, J., Hofste, T., Pfundt, R., Corominas Galbany, J., Rinne, T., Yntema, H. G., Hoischen, A., Nelen, M., Gilissen, C., Solve-RD consortium, Riess, O., Haack, T. B., Graessner, H., Zurek, B., Ellwanger, K., Ossowski, S., Demidov, G., ... et al. (2023). Twist exome capture allows for lower average sequence coverage in clinical exome sequencing. Human Genomics, 17(1), Article 39. https://doi.org/10.1186/s40246-023-00485-5

@article{15f639294f1440609dcf0a8606fb1950,

title = "Twist exome capture allows for lower average sequence coverage in clinical exome sequencing",

abstract = "Background: Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results: We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion: We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.",

keywords = "Exome sequencing, Genome sequencing, Uniformity of coverage, High-Throughput Nucleotide Sequencing/methods, Exome Sequencing, Humans, Genome, Human/genetics, Base Sequence, Exome/genetics, DNA Copy Number Variations/genetics",

author = "Burcu Yaldiz and Erdi Kucuk and Juliet Hampstead and Tom Hofste and Rolph Pfundt and {Corominas Galbany}, Jordi and Tuula Rinne and Yntema, {Helger G.} and Alexander Hoischen and Marcel Nelen and Christian Gilissen and {Solve-RD consortium} and Olaf Riess and Haack, {Tobias B.} and Holm Graessner and Birte Zurek and Kornelia Ellwanger and Stephan Ossowski and German Demidov and Marc Sturm and Schulze-Hentrich, {Julia M.} and Rebecca Sch{\"u}le and Jishu Xu and Christoph Kessler and Melanie Wayand and Matthis Synofzik and Carlo Wilke and Andreas Trasch{\"u}tz and Ludger Sch{\"o}ls and Holger Hengel and Holger Lerche and Josua Kegele and Peter Heutink and Han Brunner and Hans Scheffer and Nicoline Hoogerbrugge and Alexander Hoischen and Hoen, {Peter A.C.{\textquoteright}t} and Vissers, {Lisenka E.L.M.} and Christian Gilissen and Wouter Steyaert and Karolis Sablauskas and {de Voer}, {Richarda M.} and Kamsteeg, {Erik Jan} and {van de Warrenburg}, Bart and {van Os}, Nienke and {te Paske}, Iris and Erik Janssen and Jill Clayton-Smith and Siddharth Banka and Adam Jackson and {et al.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1186/s40246-023-00485-5",

language = "English",

volume = "17",

journal = "Human Genomics",

issn = "1473-9542",

publisher = "Springer Nature",

number = "1",

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Yaldiz, B, Kucuk, E, Hampstead, J, Hofste, T, Pfundt, R, Corominas Galbany, J, Rinne, T, Yntema, HG, Hoischen, A, Nelen, M, Gilissen, C, Solve-RD consortium, Riess, O, Haack, TB, Graessner, H, Zurek, B, Ellwanger, K, Ossowski, S, Demidov, G, Sturm, M, Schulze-Hentrich, JM, Schüle, R, Xu, J, Kessler, C, Wayand, M, Synofzik, M, Wilke, C, Traschütz, A, Schöls, L, Hengel, H, Lerche, H, Kegele, J, Heutink, P, Brunner, H, Scheffer, H, Hoogerbrugge, N, Hoischen, A, Hoen, PAC, Vissers, LELM, Gilissen, C, Steyaert, W, Sablauskas, K, de Voer, RM, Kamsteeg, EJ, van de Warrenburg, B, van Os, N, te Paske, I, Janssen, E, Clayton-Smith, J, Banka, S, Jackson, A & et al. 2023, 'Twist exome capture allows for lower average sequence coverage in clinical exome sequencing', Human Genomics, vol. 17, no. 1, 39. https://doi.org/10.1186/s40246-023-00485-5

TY - JOUR

T1 - Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

AU - Yaldiz, Burcu

AU - Kucuk, Erdi

AU - Hampstead, Juliet

AU - Hofste, Tom

AU - Pfundt, Rolph

AU - Corominas Galbany, Jordi

AU - Rinne, Tuula

AU - Yntema, Helger G.

AU - Hoischen, Alexander

AU - Nelen, Marcel

AU - Gilissen, Christian

AU - Solve-RD consortium

AU - Riess, Olaf

AU - Haack, Tobias B.

AU - Graessner, Holm

AU - Zurek, Birte

AU - Ellwanger, Kornelia

AU - Ossowski, Stephan

AU - Demidov, German

AU - Sturm, Marc

AU - Schulze-Hentrich, Julia M.

AU - Schüle, Rebecca

AU - Xu, Jishu

AU - Kessler, Christoph

AU - Wayand, Melanie

AU - Synofzik, Matthis

AU - Wilke, Carlo

AU - Traschütz, Andreas

AU - Schöls, Ludger

AU - Hengel, Holger

AU - Lerche, Holger

AU - Kegele, Josua

AU - Heutink, Peter

AU - Brunner, Han

AU - Scheffer, Hans

AU - Hoogerbrugge, Nicoline

AU - Hoischen, Alexander

AU - Hoen, Peter A.C.’t

AU - Vissers, Lisenka E.L.M.

AU - Gilissen, Christian

AU - Steyaert, Wouter

AU - Sablauskas, Karolis

AU - de Voer, Richarda M.

AU - Kamsteeg, Erik Jan

AU - van de Warrenburg, Bart

AU - van Os, Nienke

AU - te Paske, Iris

AU - Janssen, Erik

AU - Clayton-Smith, Jill

AU - Banka, Siddharth

AU - Jackson, Adam

AU - et al.,

PY - 2023/12

Y1 - 2023/12

N2 - Background: Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results: We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion: We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.

AB - Background: Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results: We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion: We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques.

KW - Exome sequencing

KW - Genome sequencing

KW - Uniformity of coverage

KW - High-Throughput Nucleotide Sequencing/methods

KW - Exome Sequencing

KW - Humans

KW - Genome, Human/genetics

KW - Base Sequence

KW - Exome/genetics

KW - DNA Copy Number Variations/genetics

UR - http://www.scopus.com/inward/record.url?scp=85158030412&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/a495c011-1d1c-3b12-83e3-9439b2ff7c0d/

U2 - 10.1186/s40246-023-00485-5

DO - 10.1186/s40246-023-00485-5

M3 - Article

C2 - 37138343

AN - SCOPUS:85158030412

SN - 1473-9542

VL - 17

JO - Human Genomics

JF - Human Genomics

IS - 1

M1 - 39

ER -

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Abstract

Keywords

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