Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.

Paired-end sequencing is emerging as a key technique for assessing genome rearrangements and structural variation on a genome-wide scale. This technique is particularly useful for detecting copy-neutral rearrangements, such as inversions and translocations, which are common in cancer and can produce...

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Autores principales:	Ali Bashir, Stanislav Volik, Colin Collins, Vineet Bafna, Benjamin J Raphael
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a2f362f5a34b4d5685a84b62578c408b
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spelling	oai:doaj.org-article:a2f362f5a34b4d5685a84b62578c408b2021-11-25T05:41:19ZEvaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.1553-734X1553-735810.1371/journal.pcbi.1000051https://doaj.org/article/a2f362f5a34b4d5685a84b62578c408b2008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18404202/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Paired-end sequencing is emerging as a key technique for assessing genome rearrangements and structural variation on a genome-wide scale. This technique is particularly useful for detecting copy-neutral rearrangements, such as inversions and translocations, which are common in cancer and can produce novel fusion genes. We address the question of how much sequencing is required to detect rearrangement breakpoints and to localize them precisely using both theoretical models and simulation. We derive a formula for the probability that a fusion gene exists in a cancer genome given a collection of paired-end sequences from this genome. We use this formula to compute fusion gene probabilities in several breast cancer samples, and we find that we are able to accurately predict fusion genes in these samples with a relatively small number of fragments of large size. We further demonstrate how the ability to detect fusion genes depends on the distribution of gene lengths, and we evaluate how different parameters of a sequencing strategy impact breakpoint detection, breakpoint localization, and fusion gene detection, even in the presence of errors that suggest false rearrangements. These results will be useful in calibrating future cancer sequencing efforts, particularly large-scale studies of many cancer genomes that are enabled by next-generation sequencing technologies.Ali BashirStanislav VolikColin CollinsVineet BafnaBenjamin J RaphaelPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 4, p e1000051 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ali Bashir Stanislav Volik Colin Collins Vineet Bafna Benjamin J Raphael Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
description	Paired-end sequencing is emerging as a key technique for assessing genome rearrangements and structural variation on a genome-wide scale. This technique is particularly useful for detecting copy-neutral rearrangements, such as inversions and translocations, which are common in cancer and can produce novel fusion genes. We address the question of how much sequencing is required to detect rearrangement breakpoints and to localize them precisely using both theoretical models and simulation. We derive a formula for the probability that a fusion gene exists in a cancer genome given a collection of paired-end sequences from this genome. We use this formula to compute fusion gene probabilities in several breast cancer samples, and we find that we are able to accurately predict fusion genes in these samples with a relatively small number of fragments of large size. We further demonstrate how the ability to detect fusion genes depends on the distribution of gene lengths, and we evaluate how different parameters of a sequencing strategy impact breakpoint detection, breakpoint localization, and fusion gene detection, even in the presence of errors that suggest false rearrangements. These results will be useful in calibrating future cancer sequencing efforts, particularly large-scale studies of many cancer genomes that are enabled by next-generation sequencing technologies.
format	article
author	Ali Bashir Stanislav Volik Colin Collins Vineet Bafna Benjamin J Raphael
author_facet	Ali Bashir Stanislav Volik Colin Collins Vineet Bafna Benjamin J Raphael
author_sort	Ali Bashir
title	Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
title_short	Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
title_full	Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
title_fullStr	Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
title_full_unstemmed	Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
title_sort	evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/a2f362f5a34b4d5685a84b62578c408b
work_keys_str_mv	AT alibashir evaluationofpairedendsequencingstrategiesfordetectionofgenomerearrangementsincancer AT stanislavvolik evaluationofpairedendsequencingstrategiesfordetectionofgenomerearrangementsincancer AT colincollins evaluationofpairedendsequencingstrategiesfordetectionofgenomerearrangementsincancer AT vineetbafna evaluationofpairedendsequencingstrategiesfordetectionofgenomerearrangementsincancer AT benjaminjraphael evaluationofpairedendsequencingstrategiesfordetectionofgenomerearrangementsincancer
_version_	1718414534320848896

Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.

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