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

P Chandrani, V Kulkarni, P Iyer, P Upadhyay… - British journal of …, 2015 - nature.com
P Chandrani, V Kulkarni, P Iyer, P Upadhyay, R Chaubal, P Das, R Mulherkar, R Singh
British journal of cancer, 2015nature.com
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 …
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.
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