NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome

Br J Cancer. 2015 Jun 9;112(12):1958-65. doi: 10.1038/bjc.2015.121. Epub 2015 May 14.

Abstract

Background: Human papilloma virus (HPV) accounts for the most common cause of all virus-associated human cancers. Here, we describe the first graphic user interface (GUI)-based automated tool 'HPVDetector', for non-computational biologists, exclusively for detection and annotation of the HPV genome based on next-generation sequencing data sets.

Methods: We developed a custom-made reference genome that comprises of human chromosomes along with annotated genome of 143 HPV types as pseudochromosomes. The tool runs on a dual mode as defined by the user: a 'quick mode' to identify presence of HPV types and an 'integration mode' to determine genomic location for the site of integration. The input data can be a paired-end whole-exome, whole-genome or whole-transcriptome data set. The HPVDetector is available in public domain for download: http://www.actrec.gov.in/pi-webpages/AmitDutt/HPVdetector/HPVDetector.html.

Results: On the basis of our evaluation of 116 whole-exome, 23 whole-transcriptome and 2 whole-genome data, we were able to identify presence of HPV in 20 exomes and 4 transcriptomes of cervical and head and neck cancer tumour samples. Using the inbuilt annotation module of HPVDetector, we found predominant integration of viral gene E7, a known oncogene, at known 17q21, 3q27, 7q35, Xq28 and novel sites of integration in the human genome. Furthermore, co-infection with high-risk HPVs such as 16 and 31 were found to be mutually exclusive compared with low-risk HPV71.

Conclusions: HPVDetector is a simple yet precise and robust tool for detecting HPV from tumour samples using variety of next-generation sequencing platforms including whole genome, whole exome and transcriptome. Two different modes (quick detection and integration mode) along with a GUI widen the usability of HPVDetector for biologists and clinicians with minimal computational knowledge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human
  • Female
  • Genome, Human*
  • Genome, Viral
  • Genomics / methods
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / virology*
  • Humans
  • Papillomaviridae / genetics*
  • Papillomaviridae / isolation & purification
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / virology*
  • Virus Integration / genetics*