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The landscape of viral associations in human cancers
Marc Zapatka, Ivan Borozan, Daniel S. Brewer, Murat Iskar, Adam Grundhoff, Malik Alawi, Holger Sültmann, Holger Moch, Nikita Desai, Roland Eils, Vincent Ferretti, Kortine Kleinheinz, Peter Lichter, Hidewaki Nakagawa, Akinyemi I. Ojesina, Chandra Sekhar Pedamallu, Matthias Schlesner, Colin S. Cooper, Lauri A. Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J. Adams, Nishant Agrawal, Keun Soo Ahn, Sung‐Min Ahn, Hiroshi Aikata, Rehan Akbani, Kadir C. Akdemir, Hikmat Al‐Ahmadie, Sultan T. Al‐Sedairy, Fátima Al‐Shahrour, Monique Albert, Kenneth Aldape, Ludmil B. Alexandrov, Adrian Ally, Kathryn Alsop, Eva G. Álvarez, Fernanda Amary, Samirkumar B. Amin, Brice Aminou, Ole Ammerpohl, Matthew J. Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparício, Elizabeth L. Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun‐ichi Ariizumi, Joshua Armenia, Laurent Arnould, L. Sylvia, Yassen Assenov, Gurnit Atwal, Sietse Aukema, J. Todd Auman, Miriam R. R. Aure, Philip Awadalla, Marta Aymerich, Gary D. Bader, Adrian Baez‐Ortega, Peter J. Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E. Banks, Stefano Barbi, Andrew P. Barbour, Jonathan Barenboim, Jill S. Barnholtz‐Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolomé, Claudio Bassi, Oliver F. Bathe, Daniel Baumhoer, Prashant Bavi, Stephen B. Baylin, Wojciech Bażant, Duncan Beardsmore, Tim Beck, Sam Behjati, Andreas Behren, Beifang Niu, Cindy Bell, Sergi Beltrán, Christopher C. Benz, Andrew Berchuck, Anke Bergmann, Erik N. Bergstrom, Benjamin P. Berman, Daniel M. Berney, Rameen Beroukhim, Mario Berríos, Samantha Bersani, Johanna Bertl, Miguel Betancourt, Vinayak Bhandari, Shriram G. Bhosle, Andrew V. Biankin, Matthias Bieg, Darell D. Bigner, Hans Binder, Ewan Birney, Michael J. Birrer, Nidhan K. Biswas, Bodil Bjerkehagen, Tom Bodenheimer, Lori Boice, Giada Bonizzato, Johann S. de Bono, Arnoud Boot, Åke Borg, Arndt Borkhardt, Keith A. 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Robert O’Neill, David Ocaña, Angelica Ochoa, Layla Oesper, Christopher Ogden, Hideki Ohdan, Kazuhiro Ohi, Lucila Ohno‐Machado, Karin A. Oien, Hidenori Ojima, Takuji Okusaka, Larsson Omberg, Choon Kiat Ong, Stephan Ossowski, German Ott, B. F. Francis Ouellette, Christine P’ng, Marta Paczkowska, Salvatore Paiella, Chawalit Pairojkul, Marina Pajic, Qiang Pan‐Hammarström, Elli Papaemmanuil, Irene Papatheodorou, Nagarajan Paramasivam, Ji Wan Park, Joong-Won Park, Keunchil Park, Kiejung Park, Peter J. Park, Joel S. Parker, Simon L. Parsons, Harvey I. Pass, Danielle Pasternack, Alessandro Pastore, Ann‐Marie Patch, Iris Pauporté, Antonio Pea, John V. Pearson, Jakob Skou Pedersen, Paolo Pederzoli, Martin Peifer, Nathan A. Pennell, Charles M. Perou, Marc D. Perry, Gloria M. Petersen, Myron Peto, Nicholas J. Petrelli, Robert Petryszak, Stefan M. Pfister, Mark Phillips, Oriol Pich, Hilda A. Pickett, Todd Pihl, Nischalan Pillay, Sarah E. Pinder, Mark Pinese, Andreia V. 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Bibliographic record
VenueNature Genetics · 2020
Typearticle
Languageen
FieldMedicine
TopicViral-associated cancers and disorders
Canadian institutionsSickKids FoundationBC Cancer AgencyUniversity of British ColumbiaProstate Cancer CanadaSimon Fraser UniversityUniversity of OttawaMcGill UniversityLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalPrincess Margaret Cancer CentreUniversity of CalgaryVector InstituteUniversity of TorontoMcGill University and Génome Québec Innovation CentreToronto General HospitalUniversity Health NetworkGenome CanadaCanada's Michael Smith Genome Sciences CentreHospital for Sick ChildrenUniversité de MontréalInstitute of Cancer ResearchOntario Institute for Cancer Research
FundersLeibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-InstitutNational Institute of Environmental Health SciencesNational Cancer InstituteBiotechnology and Biological Sciences Research CouncilBundesministerium für Bildung und ForschungSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungLeibniz-GemeinschaftGovernment of OntarioCancer Research UKNational Science FoundationOntario Institute for Cancer ResearchDeutsches Zentrum für InfektionsforschungDeutsches KrebsforschungszentrumFrancis Crick Institute
KeywordsBiologyAPOBECTranscriptomeHepatitis B virusGenomeVirologyVirusCancerMerkel cell polyomavirusEndogenous retrovirusGeneticsGeneCancer researchCarcinomaMerkel cell carcinomaGene expression
Abstract
Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and-for a subset-whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein-Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.021
Threshold uncertainty score0.199
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.010
GPT teacher head0.282
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations403
Published2020
Admission routes2
Has abstractyes