Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma

Abstract Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural v...

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Autores principales:	Hannah E. Roberts, Maria Lopopolo, Alistair T. Pagnamenta, Eshita Sharma, Duncan Parkes, Lorne Lonie, Colin Freeman, Samantha J. L. Knight, Gerton Lunter, Helene Dreau, Helen Lockstone, Jenny C. Taylor, Anna Schuh, Rory Bowden, David Buck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e945e04ccd3245778164376c6ae22f52
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spelling	oai:doaj.org-article:e945e04ccd3245778164376c6ae22f522021-12-02T13:18:00ZShort and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma10.1038/s41598-021-85354-82045-2322https://doaj.org/article/e945e04ccd3245778164376c6ae22f522021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85354-8https://doaj.org/toc/2045-2322Abstract Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.Hannah E. RobertsMaria LopopoloAlistair T. PagnamentaEshita SharmaDuncan ParkesLorne LonieColin FreemanSamantha J. L. KnightGerton LunterHelene DreauHelen LockstoneJenny C. TaylorAnna SchuhRory BowdenDavid BuckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hannah E. Roberts Maria Lopopolo Alistair T. Pagnamenta Eshita Sharma Duncan Parkes Lorne Lonie Colin Freeman Samantha J. L. Knight Gerton Lunter Helene Dreau Helen Lockstone Jenny C. Taylor Anna Schuh Rory Bowden David Buck Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
description	Abstract Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.
format	article
author	Hannah E. Roberts Maria Lopopolo Alistair T. Pagnamenta Eshita Sharma Duncan Parkes Lorne Lonie Colin Freeman Samantha J. L. Knight Gerton Lunter Helene Dreau Helen Lockstone Jenny C. Taylor Anna Schuh Rory Bowden David Buck
author_facet	Hannah E. Roberts Maria Lopopolo Alistair T. Pagnamenta Eshita Sharma Duncan Parkes Lorne Lonie Colin Freeman Samantha J. L. Knight Gerton Lunter Helene Dreau Helen Lockstone Jenny C. Taylor Anna Schuh Rory Bowden David Buck
author_sort	Hannah E. Roberts
title	Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
title_short	Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
title_full	Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
title_fullStr	Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
title_full_unstemmed	Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma
title_sort	short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large b-cell lymphoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e945e04ccd3245778164376c6ae22f52
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Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma

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