Friday, 9 October 2015

#ABACBS Poster FF6: Evidence for viral causes of cancer in prostate cancer transcriptomes and genomes

Timothy G. Amos, James S. Lawson, Wendy K. Glenn, Noel J. Whitaker & Richard J. Edwards.


Viruses are known to cause 10-15% of human cancers. Some ongoing viral infections such as HPV in cervical cancer can be easily detected in the cancer transcriptome. However, in other situations viruses contribute to cancer causation without sustained high expression levels. PCR has detected HPV in prostate cancers but RNA-Seq has not shown strong evidence of continuing infections. We analysed prostate cancer transcriptomes and genomes from The Cancer Genome Atlas to further investigate HPV’s role in prostate cancer causation. Previous studies have filtered out all reads that might not be viral and then set thresholds for real infections by comparing to positive controls. In contrast, we found all possible viral reads and then evaluated multiple streams of evidence that they were genuine. Sequences were evaluated on the uniqueness of alignments to human, viral and vector sequences. They were also evaluated for sequence complexity, sequence quality, alignment quality, relative alignment locations of paired-end reads and the presence of chimeric reads that indicate viral integration sites. By screening cancer transcriptomes and genomes against all viruses in the NCBI database (c. N = 5766), including non-human viruses, we are also able to compare the strength of evidence against known false positives. We discuss the results of 22 viral candidates for oncogenesis in 558 prostate cancer paired RNA-Seq and WGS datasets.

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