Investigation of human cancers for retrovirus by low-stringency target enrichment and high-throughput sequencing

Lasse Vinner; Tobias Mourier; Jens Friis-Nielsen; Robert Gniadecki; Karen Dybkaer; Jacob Rosenberg; Jill Levin Langhoff; David Flores Santa Cruz; Jannik Fonager; Jose M. G. Izarzugaza; Ramneek Gupta; Thomas Sicheritz-Ponten; Søren Brunak; Eske Willerslev; Lars Peter Nielsen; Anders Johannes Hansen

doi:10.1038/srep13201

Investigation of human cancers for retrovirus by low-stringency target enrichment and high-throughput sequencing

Lasse Vinner, Tobias Mourier, Jens Friis-Nielsen, Robert Gniadecki, Karen Dybkaer, Jacob Rosenberg, Jill Levin Langhoff, David Flores Santa Cruz, Jannik Fonager, Jose M. G. Izarzugaza, Ramneek Gupta, Thomas Sicheritz-Ponten, Søren Brunak, Eske Willerslev, Lars Peter Nielsen, Anders Johannes Hansen

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Abstract

Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.

Original language	English
Article number	13201
Journal	Scientific Reports
Volume	5
Number of pages	13
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep13201
Publication status	Published - 19 Aug 2015

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Vinner, L., Mourier, T., Friis-Nielsen, J., Gniadecki, R., Dybkaer, K., Rosenberg, J., Langhoff, J. L., Flores Santa Cruz, D., Fonager, J., Izarzugaza, J. M. G., Gupta, R., Sicheritz-Ponten, T., Brunak, S., Willerslev, E., Nielsen, L. P., & Hansen, A. J. (2015). Investigation of human cancers for retrovirus by low-stringency target enrichment and high-throughput sequencing. Scientific Reports, 5, [13201]. https://doi.org/10.1038/srep13201

Vinner, L, Mourier, T, Friis-Nielsen, J, Gniadecki, R, Dybkaer, K, Rosenberg, J, Langhoff, JL, Flores Santa Cruz, D, Fonager, J, Izarzugaza, JMG, Gupta, R, Sicheritz-Ponten, T, Brunak, S , Willerslev, E, Nielsen, LP & Hansen, AJ 2015, 'Investigation of human cancers for retrovirus by low-stringency target enrichment and high-throughput sequencing', Scientific Reports, vol. 5, 13201. https://doi.org/10.1038/srep13201

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title = "Investigation of human cancers for retrovirus by low-stringency target enrichment and high-throughput sequencing",

abstract = "Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.",

author = "Lasse Vinner and Tobias Mourier and Jens Friis-Nielsen and Robert Gniadecki and Karen Dybkaer and Jacob Rosenberg and Langhoff, {Jill Levin} and {Flores Santa Cruz}, David and Jannik Fonager and Izarzugaza, {Jose M. G.} and Ramneek Gupta and Thomas Sicheritz-Ponten and S{\o}ren Brunak and Eske Willerslev and Nielsen, {Lars Peter} and Hansen, {Anders Johannes}",

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AU - Vinner, Lasse

AU - Mourier, Tobias

AU - Friis-Nielsen, Jens

AU - Gniadecki, Robert

AU - Dybkaer, Karen

AU - Rosenberg, Jacob

AU - Langhoff, Jill Levin

AU - Flores Santa Cruz, David

AU - Fonager, Jannik

AU - Izarzugaza, Jose M. G.

AU - Gupta, Ramneek

AU - Sicheritz-Ponten, Thomas

AU - Brunak, Søren

AU - Willerslev, Eske

AU - Nielsen, Lars Peter

AU - Hansen, Anders Johannes

PY - 2015/8/19

Y1 - 2015/8/19

N2 - Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.

AB - Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific, and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of <100 viral copies. Furthermore, distantly related proviral sequences may be enriched by orders of magnitude, enabling discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer biopsies. Nonetheless, our generally applicable method makes sensitive detection possible and permits sequencing of distantly related sequences from complex material.

U2 - 10.1038/srep13201

DO - 10.1038/srep13201

M3 - Journal article

C2 - 26285800

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 13201

ER -

Investigation of human cancers for retrovirus by low-stringency target enrichment and high-throughput sequencing

Abstract

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