Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL

Jenny Klintman; Katerina Barmpouti; Samantha J.L. Knight; Pauline Robbe; Hélène Dreau; Ruth Clifford; Kate Ridout; Adam Burns; Adele Timbs; David Bruce; Pavlos Antoniou; Alona Sosinsky; Jennifer Becq; David Bentley; Peter Hillmen; Jenny C. Taylor; Mark Caulfield; Anna H. Schuh

doi:10.1111/bjh.15406

Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL

Jenny Klintman
, Katerina Barmpouti
, Samantha J.L. Knight
, Pauline Robbe
, Hélène Dreau
, Ruth Clifford
, Kate Ridout
, Adam Burns
, Adele Timbs
, David Bruce
, Pavlos Antoniou
, Alona Sosinsky
, Jennifer Becq
, David Bentley
, Peter Hillmen
, Jenny C. Taylor
, Mark Caulfield
, Anna H. Schuh

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

Abstract

The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.

Original language	English
Pages (from-to)	412-417
Number of pages	6
Journal	British Journal of Haematology
Volume	182
Issue number	3
DOIs	https://doi.org/10.1111/bjh.15406
Publication status	Published - Aug 2018
Externally published	Yes

Keywords

CLL
Genomics England
chronic lymphocytic leukaemia
precision medicine
whole genome sequencing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/bjh.15406

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Klintman, J., Barmpouti, K., Knight, S. J. L., Robbe, P., Dreau, H., Clifford, R., Ridout, K., Burns, A., Timbs, A., Bruce, D., Antoniou, P., Sosinsky, A., Becq, J., Bentley, D., Hillmen, P., Taylor, J. C., Caulfield, M., & Schuh, A. H. (2018). Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL. British Journal of Haematology, 182(3), 412-417. https://doi.org/10.1111/bjh.15406

@article{ba45e0d29a61490ab69a220e9703d2b4,

title = "Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL",

abstract = "The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3\%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7\% and 92·9\%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.",

keywords = "CLL, Genomics England, chronic lymphocytic leukaemia, precision medicine, whole genome sequencing",

author = "Jenny Klintman and Katerina Barmpouti and Knight, \{Samantha J.L.\} and Pauline Robbe and H{\'e}l{\`e}ne Dreau and Ruth Clifford and Kate Ridout and Adam Burns and Adele Timbs and David Bruce and Pavlos Antoniou and Alona Sosinsky and Jennifer Becq and David Bentley and Peter Hillmen and Taylor, \{Jenny C.\} and Mark Caulfield and Schuh, \{Anna H.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Crown copyright. British Journal of Haematology {\textcopyright} 2018 John Wiley \& Sons Ltd and British Society for Haematology",

year = "2018",

month = aug,

doi = "10.1111/bjh.15406",

language = "English",

volume = "182",

pages = "412--417",

journal = "British Journal of Haematology",

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Klintman, J, Barmpouti, K, Knight, SJL, Robbe, P, Dreau, H, Clifford, R, Ridout, K, Burns, A, Timbs, A, Bruce, D, Antoniou, P, Sosinsky, A, Becq, J, Bentley, D, Hillmen, P, Taylor, JC, Caulfield, M & Schuh, AH 2018, 'Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL', British Journal of Haematology, vol. 182, no. 3, pp. 412-417. https://doi.org/10.1111/bjh.15406

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T1 - Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL

AU - Klintman, Jenny

AU - Barmpouti, Katerina

AU - Knight, Samantha J.L.

AU - Robbe, Pauline

AU - Dreau, Hélène

AU - Clifford, Ruth

AU - Ridout, Kate

AU - Burns, Adam

AU - Timbs, Adele

AU - Bruce, David

AU - Antoniou, Pavlos

AU - Sosinsky, Alona

AU - Becq, Jennifer

AU - Bentley, David

AU - Hillmen, Peter

AU - Taylor, Jenny C.

AU - Caulfield, Mark

AU - Schuh, Anna H.

PY - 2018/8

Y1 - 2018/8

N2 - The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.

AB - The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected to WGS. WGS detection of single nucleotide variants and insertion/deletions were validated by targeted next generation sequencing showing high concordance (96·3%), also for detection of sub-clonal variants and low-frequency TP53 variants. Copy number alteration detection was verified by fluorescent in situ hybridisation and genome-wide single nucleotide polymorphism array (concordances of 86·7% and 92·9%, respectively), confirming adequate sensitivity by WGS. Our results confirm that WGS can provide comprehensive genomic characterisation for clinical trials, drug discovery and, ultimately, precision medicine.

KW - CLL

KW - Genomics England

KW - chronic lymphocytic leukaemia

KW - precision medicine

KW - whole genome sequencing

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DO - 10.1111/bjh.15406

M3 - Article

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SN - 0007-1048

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SP - 412

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JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 3

ER -

Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL

Abstract

Keywords

UN SDGs

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