Universität zu Köln

Schelhorn, Sven-Eric, Fischer, Matthias, Tolosi, Laura, Altmueller, Janine, Nuernberg, Peter, Pfister, Herbert, Lengauer, Thomas and Berthold, Frank (2013). Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes. PLoS Comput. Biol., 9 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7358

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Abstract

In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates analyzed. Therefore, our results suggest that frequent viral cofactors of metastatic neuroblastoma are unlikely.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schelhorn, Sven-Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Tolosi, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Lengauer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Berthold, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-474331
DOI:	10.1371/journal.pcbi.1003228
Journal or Publication Title:	PLoS Comput. Biol.
Volume:	9
Number:	10
Date:	2013
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7358
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPSTEIN-BARR-VIRUS; RNA-SEQ DATA; MERKEL CELL-CARCINOMA; HUMAN CANCER; KAPOSIS-SARCOMA; GENE-EXPRESSION; HUMAN-PAPILLOMAVIRUS; FUSION TRANSCRIPTS; HUMAN TISSUE; HUMAN GENOME Multiple languages Biochemical Research Methods; Mathematical & Computational Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47433