Poster Presentation 39th Annual Lorne Genome Conference 2018

Identifying Hepatitis B virus integration events on Mouse genome (#107)

Waruni Abeysekera 1 2 , Zina Valaydon 1 3 4 , Marc Pellegrini 1 2 , Gordon Smyth 1 5
  1. Walter and Eliza Hall Institute of Medical Research, Melbourne, VICTORIA, Australia
  2. Department of Medical Biology, The University of Melbourne, Parkville, VICTORIA, Australia
  3. Department of Medicine, Eastern Hill Academic Centre , The University of Melbourne, Parkville, VICTORIA, Australia
  4. Department of Gastroenterology, St Vincent's Hospital, Fitzroy, VICTORIA, Australia
  5. School of Mathematics and Statistics, The University of Melbourne, Parkville, VICTORIA, Australia

Hepatitis B virus (HBV) causes the most common liver infection and is known as a leading risk factor for liver cirrhosis and hepatocellular carcinoma. More than 300 million people worldwide are estimated to be infected with this virus. HBV is a double stranded DNA virus of the family Hepadnaviridae that has the ability to integrate into host chromosomes when infected. The mechanism of the HBV DNA integration into host genome remains ambiguous, yet it is believed that this integration occurs during the virus replication. Here, we describe two approaches to identify HBV integration events in the mouse genome using RNA sequencing (RNA-Seq) data of HBV infected mouse liver samples.  In the first approach, raw paired-end (PE) reads of RNA-Seq data are mapped to a hybrid reference genome built by concatenating mouse mm10 genome and HBV genome. A uniquely mapped of a PE read with one end mapped to mouse genome and the other end mapped to HBV genome is classified as a mouse-HBV chimeric PE read and is considered as an identified virus integration event. Such chimeric reads/integration events are annotated by Ref-Seq gene annotation and reads with same integration events are clustered together. Approach 2 consists of two step alignment of the RNA-Seq data, where the chimeric PE reads are identified by first mapping PE reads to the HBV genome, and the resulting mapped viral reads are then re-mapped to the mouse genome. These two approaches are illustrated by an RNA-Seq data of 12 mouse liver samples infected with 3 conditions of HBV, namely precore mutant, basal core promoter mutant and wild type.