High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach

Sarah Mollerup; Maria Asplund; Jens Friis-Nielsen; Kristín Rós Kjartansdóttir; Helena Fridholm; Thomas Arn Hansen; José Alejandro Romero Herrera; Christopher James Barnes; Randi Holm Jensen; Stine Raith Richter; Ida Broman Nielsen; Carlotta Pietroni; David E Alquezar-Planas; Alba Rey-Iglesia; Pernille V S Olsen; Ewa Rajpert-De Meyts; Line Groth-Pedersen; Christian von Buchwald; David H Jensen; Robert Gniadecki; Estrid Høgdall; Jill Levin Langhoff; Imre Pete; Ildikó Vereczkey; Zsolt Baranyai; Karen Dybkaer; Hans Erik Johnsen; Torben Steiniche; Peter Hokland; Jacob Rosenberg; Ulrik Baandrup; Thomas Sicheritz-Pontén; Eske Willerslev; Søren Brunak; Ole Lund; Tobias Mourier; Lasse Vinner; Jose M G Izarzugaza; Lars Peter Nielsen; Anders Johannes Hansen

doi:10.1093/infdis/jiz318

High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach

Sarah Mollerup, Maria Asplund, Jens Friis-Nielsen, Kristín Rós Kjartansdóttir, Helena Fridholm, Thomas Arn Hansen, José Alejandro Romero Herrera, Christopher James Barnes, Randi Holm Jensen, Stine Raith Richter, Ida Broman Nielsen, Carlotta Pietroni, David E Alquezar-Planas, Alba Rey-Iglesia, Pernille V S Olsen, Ewa Rajpert-De Meyts, Line Groth-Pedersen, Christian von Buchwald, David H Jensen, Robert GniadeckiEstrid Høgdall, Jill Levin Langhoff, Imre Pete, Ildikó Vereczkey, Zsolt Baranyai, Karen Dybkaer, Hans Erik Johnsen, Torben Steiniche, Peter Hokland, Jacob Rosenberg, Ulrik Baandrup, Thomas Sicheritz-Pontén, Eske Willerslev, Søren Brunak, Ole Lund, Tobias Mourier, Lasse Vinner, Jose M G Izarzugaza, Lars Peter Nielsen, Anders Johannes Hansen

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Abstract

BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.

METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.

RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.

CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

Original language	English
Journal	The Journal of Infectious Diseases
Volume	220
Issue number	8
Pages (from-to)	1312-1324
ISSN	0022-1899
DOIs	https://doi.org/10.1093/infdis/jiz318
Publication status	Published - 13 Sept 2019

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High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment ApproachFinal published version, 879 KBLicence: CC BY

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Mollerup, S., Asplund, M., Friis-Nielsen, J., Kjartansdóttir, K. R., Fridholm, H., Hansen, T. A., Herrera, J. A. R., Barnes, C. J., Jensen, R. H., Richter, S. R., Nielsen, I. B., Pietroni, C., Alquezar-Planas, D. E., Rey-Iglesia, A., Olsen, P. V. S., Rajpert-De Meyts, E., Groth-Pedersen, L., von Buchwald, C., Jensen, D. H., ... Hansen, A. J. (2019). High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach. The Journal of Infectious Diseases, 220(8), 1312-1324. https://doi.org/10.1093/infdis/jiz318

Mollerup, S, Asplund, M, Friis-Nielsen, J, Kjartansdóttir, KR, Fridholm, H, Hansen, TA, Herrera, JAR, Barnes, CJ, Jensen, RH, Richter, SR, Nielsen, IB , Pietroni, C, Alquezar-Planas, DE, Rey-Iglesia, A , Olsen, PVS, Rajpert-De Meyts, E, Groth-Pedersen, L, von Buchwald, C, Jensen, DH, Gniadecki, R, Høgdall, E, Langhoff, JL, Pete, I, Vereczkey, I, Baranyai, Z, Dybkaer, K, Johnsen, HE, Steiniche, T, Hokland, P, Rosenberg, J, Baandrup, U, Sicheritz-Pontén, T , Willerslev, E , Brunak, S, Lund, O, Mourier, T, Vinner, L, Izarzugaza, JMG, Nielsen, LP & Hansen, AJ 2019, 'High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach', The Journal of Infectious Diseases, vol. 220, no. 8, pp. 1312-1324. https://doi.org/10.1093/infdis/jiz318

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title = "High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach",

abstract = "BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.",

author = "Sarah Mollerup and Maria Asplund and Jens Friis-Nielsen and Kjartansd{\'o}ttir, {Krist{\'i}n R{\'o}s} and Helena Fridholm and Hansen, {Thomas Arn} and Herrera, {Jos{\'e} Alejandro Romero} and Barnes, {Christopher James} and Jensen, {Randi Holm} and Richter, {Stine Raith} and Nielsen, {Ida Broman} and Carlotta Pietroni and Alquezar-Planas, {David E} and Alba Rey-Iglesia and Olsen, {Pernille V S} and {Rajpert-De Meyts}, Ewa and Line Groth-Pedersen and {von Buchwald}, Christian and Jensen, {David H} and Robert Gniadecki and Estrid H{\o}gdall and Langhoff, {Jill Levin} and Imre Pete and Ildik{\'o} Vereczkey and Zsolt Baranyai and Karen Dybkaer and Johnsen, {Hans Erik} and Torben Steiniche and Peter Hokland and Jacob Rosenberg and Ulrik Baandrup and Thomas Sicheritz-Pont{\'e}n and Eske Willerslev and S{\o}ren Brunak and Ole Lund and Tobias Mourier and Lasse Vinner and Izarzugaza, {Jose M G} and Nielsen, {Lars Peter} and Hansen, {Anders Johannes}",

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doi = "10.1093/infdis/jiz318",

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T1 - High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach

AU - Mollerup, Sarah

AU - Asplund, Maria

AU - Friis-Nielsen, Jens

AU - Kjartansdóttir, Kristín Rós

AU - Fridholm, Helena

AU - Hansen, Thomas Arn

AU - Herrera, José Alejandro Romero

AU - Barnes, Christopher James

AU - Jensen, Randi Holm

AU - Richter, Stine Raith

AU - Nielsen, Ida Broman

AU - Pietroni, Carlotta

AU - Alquezar-Planas, David E

AU - Rey-Iglesia, Alba

AU - Olsen, Pernille V S

AU - Rajpert-De Meyts, Ewa

AU - Groth-Pedersen, Line

AU - von Buchwald, Christian

AU - Jensen, David H

AU - Gniadecki, Robert

AU - Høgdall, Estrid

AU - Langhoff, Jill Levin

AU - Pete, Imre

AU - Vereczkey, Ildikó

AU - Baranyai, Zsolt

AU - Dybkaer, Karen

AU - Johnsen, Hans Erik

AU - Steiniche, Torben

AU - Hokland, Peter

AU - Rosenberg, Jacob

AU - Baandrup, Ulrik

AU - Sicheritz-Pontén, Thomas

AU - Willerslev, Eske

AU - Brunak, Søren

AU - Lund, Ole

AU - Mourier, Tobias

AU - Vinner, Lasse

AU - Izarzugaza, Jose M G

AU - Nielsen, Lars Peter

AU - Hansen, Anders Johannes

PY - 2019/9/13

Y1 - 2019/9/13

N2 - BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

AB - BACKGROUND: Viruses and other infectious agents cause more than 15% of human cancer cases. High-throughput sequencing-based studies of virus-cancer associations have mainly focused on cancer transcriptome data.METHODS: In this study, we applied a diverse selection of presequencing enrichment methods targeting all major viral groups, to characterize the viruses present in 197 samples from 18 sample types of cancerous origin. Using high-throughput sequencing, we generated 710 datasets constituting 57 billion sequencing reads.RESULTS: Detailed in silico investigation of the viral content, including exclusion of viral artefacts, from de novo assembled contigs and individual sequencing reads yielded a map of the viruses detected. Our data reveal a virome dominated by papillomaviruses, anelloviruses, herpesviruses, and parvoviruses. More than half of the included samples contained 1 or more viruses; however, no link between specific viruses and cancer types were found.CONCLUSIONS: Our study sheds light on viral presence in cancers and provides highly relevant virome data for future reference.

U2 - 10.1093/infdis/jiz318

DO - 10.1093/infdis/jiz318

M3 - Journal article

C2 - 31253993

SN - 0022-1899

VL - 220

SP - 1312

EP - 1324

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

IS - 8

ER -

High-Throughput Sequencing-Based Investigation of Viruses in Human Cancers by Multienrichment Approach

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