title: NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome.
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.
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: P
authors.initials: P
authors.lastname: Chandrani
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: V
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: P
authors.initials: P
authors.lastname: Iyer
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: P
authors.initials: P
authors.lastname: Upadhyay
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: R
authors.initials: R
authors.lastname: Chaubal
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: P
authors.initials: P
authors.lastname: Das
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: R
authors.initials: R
authors.lastname: Mulherkar
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
authors.forename: A
authors.initials: A
authors.lastname: Dutt
mesh_terms: D002877:Chromosomes, Human; D005260:Female; D015894:Genome, Human; D016679:Genome, Viral; D023281:Genomics / Q000379:methods; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000821:virology*; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics* / Q000302:isolation & purification; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000821:virology*; D016662:Virus Integration / Q000235:genetics*