Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 7, Pages 3309-3325Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky180
Keywords
-
Categories
Funding
- National Science Foundation [DBI-1458557]
- National Institutes of Health (NIH) [R01GM114362]
- Extreme Science and Engineering Discovery Environment [TG-ASC160042]
- Ludwig Institute for Cancer Research
- National Institute for Neurological Diseases and Stroke [NS73831]
- Defeat GBM Program of the National Brain Tumor Society
- Ben and Catherine Ivy Foundation
- Sharpe/National Brain Tumor Society Research Program
- Ziering Family Foundation
- NIH [R01GM114362]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1458557] Funding Source: National Science Foundation
Ask authors/readers for more resources
The integration of viral sequences into the host genome is an important driver of tumorigenesis in many viral mediated cancers, notably cervical cancer and hepatocellular carcinoma. We present ViFi, a computational method that combines phylogenetic methods with reference-based read mapping to detect viral integrations. In contrast with read-based reference mapping approaches, ViFi is faster, and shows high precision and sensitivity on both simulated and biological data, even when the integrated virus is a novel strain or highly mutated. We applied ViFi to matched genomic and mRNA data from 68 cervical cancer samples from TCGA and found high concordance between the two. Surprisingly, viral integration resulted in a dramatic transcriptional upregulation in all proximal elements, including LINEs and LTRs that are not normally transcribed. This upregulation is highly correlated with the presence of a viral gene fused with a downstream human element. Moreover, genomic rearrangements suggest the formation of apparent circular extrachromosomal (ecDNA) human-viral structures. Our results suggest the presence of apparent small circular fusion viral/human ecDNA, which correlates with indiscriminate and unregulated expression of proximal genomic elements, potentially contributing to the pathogenesis of HPV-associated cervical cancers. ViFi is available at https://github.com/namphuon/ViFi.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available