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SvABA: genome-wide detection of structural variants and indels by local assembly

Structural variants (SVs), including small insertion and deletion variants (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach to identifying SVs, but is difficult to apply at scale genome-wide for SV detection du...

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Autores principales: Wala, Jeremiah A., Bandopadhayay, Pratiti, Greenwald, Noah F., O'Rourke, Ryan, Sharpe, Ted, Stewart, Chip, Schumacher, Steve, Li, Yilong, Weischenfeldt, Joachim, Yao, Xiaotong, Nusbaum, Chad, Campbell, Peter, Getz, Gad, Meyerson, Matthew, Zhang, Cheng-Zhong, Imielinski, Marcin, Beroukhim, Rameen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880247/
https://www.ncbi.nlm.nih.gov/pubmed/29535149
http://dx.doi.org/10.1101/gr.221028.117
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author Wala, Jeremiah A.
Bandopadhayay, Pratiti
Greenwald, Noah F.
O'Rourke, Ryan
Sharpe, Ted
Stewart, Chip
Schumacher, Steve
Li, Yilong
Weischenfeldt, Joachim
Yao, Xiaotong
Nusbaum, Chad
Campbell, Peter
Getz, Gad
Meyerson, Matthew
Zhang, Cheng-Zhong
Imielinski, Marcin
Beroukhim, Rameen
author_facet Wala, Jeremiah A.
Bandopadhayay, Pratiti
Greenwald, Noah F.
O'Rourke, Ryan
Sharpe, Ted
Stewart, Chip
Schumacher, Steve
Li, Yilong
Weischenfeldt, Joachim
Yao, Xiaotong
Nusbaum, Chad
Campbell, Peter
Getz, Gad
Meyerson, Matthew
Zhang, Cheng-Zhong
Imielinski, Marcin
Beroukhim, Rameen
author_sort Wala, Jeremiah A.
collection PubMed
description Structural variants (SVs), including small insertion and deletion variants (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach to identifying SVs, but is difficult to apply at scale genome-wide for SV detection due to its computational complexity and the difficulty of extracting SVs from assembly contigs. We describe SvABA, an efficient and accurate method for detecting SVs from short-read sequencing data using genome-wide local assembly with low memory and computing requirements. We evaluated SvABA's performance on the NA12878 human genome and in simulated and real cancer genomes. SvABA demonstrates superior sensitivity and specificity across a large spectrum of SVs and substantially improves detection performance for variants in the 20–300 bp range, compared with existing methods. SvABA also identifies complex somatic rearrangements with chains of short (<1000 bp) templated-sequence insertions copied from distant genomic regions. We applied SvABA to 344 cancer genomes from 11 cancer types and found that short templated-sequence insertions occur in ∼4% of all somatic rearrangements. Finally, we demonstrate that SvABA can identify sites of viral integration and cancer driver alterations containing medium-sized (50–300 bp) SVs.
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spelling pubmed-58802472018-10-01 SvABA: genome-wide detection of structural variants and indels by local assembly Wala, Jeremiah A. Bandopadhayay, Pratiti Greenwald, Noah F. O'Rourke, Ryan Sharpe, Ted Stewart, Chip Schumacher, Steve Li, Yilong Weischenfeldt, Joachim Yao, Xiaotong Nusbaum, Chad Campbell, Peter Getz, Gad Meyerson, Matthew Zhang, Cheng-Zhong Imielinski, Marcin Beroukhim, Rameen Genome Res Method Structural variants (SVs), including small insertion and deletion variants (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach to identifying SVs, but is difficult to apply at scale genome-wide for SV detection due to its computational complexity and the difficulty of extracting SVs from assembly contigs. We describe SvABA, an efficient and accurate method for detecting SVs from short-read sequencing data using genome-wide local assembly with low memory and computing requirements. We evaluated SvABA's performance on the NA12878 human genome and in simulated and real cancer genomes. SvABA demonstrates superior sensitivity and specificity across a large spectrum of SVs and substantially improves detection performance for variants in the 20–300 bp range, compared with existing methods. SvABA also identifies complex somatic rearrangements with chains of short (<1000 bp) templated-sequence insertions copied from distant genomic regions. We applied SvABA to 344 cancer genomes from 11 cancer types and found that short templated-sequence insertions occur in ∼4% of all somatic rearrangements. Finally, we demonstrate that SvABA can identify sites of viral integration and cancer driver alterations containing medium-sized (50–300 bp) SVs. Cold Spring Harbor Laboratory Press 2018-04 /pmc/articles/PMC5880247/ /pubmed/29535149 http://dx.doi.org/10.1101/gr.221028.117 Text en © 2018 Wala et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Method
Wala, Jeremiah A.
Bandopadhayay, Pratiti
Greenwald, Noah F.
O'Rourke, Ryan
Sharpe, Ted
Stewart, Chip
Schumacher, Steve
Li, Yilong
Weischenfeldt, Joachim
Yao, Xiaotong
Nusbaum, Chad
Campbell, Peter
Getz, Gad
Meyerson, Matthew
Zhang, Cheng-Zhong
Imielinski, Marcin
Beroukhim, Rameen
SvABA: genome-wide detection of structural variants and indels by local assembly
title SvABA: genome-wide detection of structural variants and indels by local assembly
title_full SvABA: genome-wide detection of structural variants and indels by local assembly
title_fullStr SvABA: genome-wide detection of structural variants and indels by local assembly
title_full_unstemmed SvABA: genome-wide detection of structural variants and indels by local assembly
title_short SvABA: genome-wide detection of structural variants and indels by local assembly
title_sort svaba: genome-wide detection of structural variants and indels by local assembly
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880247/
https://www.ncbi.nlm.nih.gov/pubmed/29535149
http://dx.doi.org/10.1101/gr.221028.117
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