title: Vy-PER: eliminating false positive detection of virus integration events in next generation sequencing data.
abstract: Several pathogenic viruses such as hepatitis B and human immunodeficiency viruses may integrate into the host genome. These virus/host integrations are detectable using paired-end next generation sequencing. However, the low number of expected true virus integrations may be difficult to distinguish from the noise of many false positive candidates. Here, we propose a novel filtering approach that increases specificity without compromising sensitivity for virus/host chimera detection. Our detection pipeline termed Vy-PER (Virus integration detection bY Paired End Reads) outperforms existing similar tools in speed and accuracy. We analysed whole genome data from childhood acute lymphoblastic leukemia (ALL), which is characterised by genomic rearrangements and usually associated with radiation exposure. This analysis was motivated by the recently reported virus integrations at genomic rearrangement sites and association with chromosomal instability in liver cancer. However, as expected, our analysis of 20 tumour and matched germline genomes from ALL patients finds no significant evidence for integrations by known viruses. Nevertheless, our method eliminates 12,800 false positives per genome (80× coverage) and only our method detects singleton human-phiX174-chimeras caused by optical errors of the Illumina HiSeq platform. This high accuracy is useful for detecting low virus integration levels as well as non-integrated viruses.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Forster
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ellinghaus
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hemmrich
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Rühlemann
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Kraemer
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Mucha
authors.affiliation: Department of Computer Science, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24118 Kiel, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Wienbrandt
authors.affiliation: Department of Pediatric Haematology and Oncology, Hannover Medical School, Lower Saxony, D-30625 Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schleswig-Holstein, D-24105 Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
mesh_terms: D019295:Computational Biology; D005189:False Positive Reactions; D015894:Genome, Human; D005854:Germ Cells / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology; D006564:Herpesviridae / Q000235:genetics / Q000502:physiology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000821:virology; D017422:Sequence Analysis, DNA; D012984:Software; D016662:Virus Integration