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.

GENE-IS: Time-Efficient and Accurate Analysis of Viral Integration Events in Large-Scale Gene Therapy Data

“…VirusFinder2.015, 16 and Vy-PER 17 were not taken into the comparison for the reasons examined in the Discussion.…”

ViR: a tool to account for intrasample variability in the detection of viral integrations

“…Host genome scaf1 scaf2 others scaf3 scaf4 [1] [2] G1 G2 G3 [3] G1 G2.3 [2] SAM file Mapped reads FASTQ [3] Host Host Virus [1] Viral genome Sample SAM file Chimeric reads txt file…”

“…Consequently, several pipelines have been developed to identify viral sequences integrated into the human genome using whole-genome sequencing (WGS) data (i.e. HIVID, SummonChimera, Vy-PER; HGT-ID, ViFi, VirTect, BS-virus-finder ) (3)(4)(5)(6)(7)(8)(9). Each of these computational methods is differentially versatile in terms of data input format (i.e.…”

VirTect: a computational method for detecting virus species from RNA-Seq and its application in head and neck squamous cell carcinoma

“…Researchers have developed some computational tools for the discovery and identification of viruses in NGS data from human tissues (3)(4)(5), including viral integration sites (6)(7)(8)(9)(10). However, all previous studies used subtractive analyses.…”