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

Author:

Mollerup Sarah1,Asplund Maria1,Friis-Nielsen Jens2,Kjartansdóttir Kristín Rós1,Fridholm Helena1,Hansen Thomas Arn1,Herrera José Alejandro Romero23,Barnes Christopher James1,Jensen Randi Holm1,Richter Stine Raith1,Nielsen Ida Broman1,Pietroni Carlotta1,Alquezar-Planas David E1,Rey-Iglesia Alba1,Olsen Pernille V S1,Rajpert-De Meyts Ewa4,Groth-Pedersen Line5,von Buchwald Christian6,Jensen David H6,Gniadecki Robert7,Høgdall Estrid8,Langhoff Jill Levin8,Pete Imre9,Vereczkey Ildikó9,Baranyai Zsolt10,Dybkaer Karen11,Johnsen Hans Erik12,Steiniche Torben13,Hokland Peter14,Rosenberg Jacob15,Baandrup Ulrik16,Sicheritz-Pontén Thomas217,Willerslev Eske1,Brunak Søren23,Lund Ole2,Mourier Tobias1,Vinner Lasse1,Izarzugaza Jose M G2,Nielsen Lars Peter18,Hansen Anders Johannes1

Affiliation:

1. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Denmark

2. Department of Bio and Health Informatics, Technical University of Denmark, Lyngby, Denmark

3. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

4. Department of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Denmark

5. Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Denmark

6. Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital

7. Department of Dermato-Venerology, Faculty of Health Sciences, Copenhagen University Hospital, Bispebjerg Hospital, Denmark

8. Department of Pathology, Herlev and Gentofte Hospital, University of Copenhagen, Denmark

9. National Institute of Oncology, Department of Gynecology, Budapest, Hungary

10. 1st Department of Surgery, Semmelweis University, Budapest, Hungary

11. Department of Clinical Medicine, Aalborg University, Denmark

12. Department of Haematology, Aalborg University Hospital, Denmark

13. Department of Pathology, Aarhus University Hospital, Denmark

14. Department of Clinical Medicine, Department of Haematology, Aarhus University Hospital, Denmark

15. Department of Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Denmark

16. Center for Clinical Research, North Denmark Regional Hospital and Department of Clinical Medicine, Aalborg University, Hjørring, Denmark

17. Centre of Excellence for Omics-Driven Computational Biodiscovery, AIMST University, Kedah, Malaysia

18. Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen S, Denmark

Abstract

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.

Funder

Innovation Fund Denmark

The GenomeDenmark platform

Danish National Research Foundation

Lundbeck Foundation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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