title: HIVID: an efficient method to detect HBV integration using low coverage sequencing.
abstract: We reported HIVID (high-throughput Viral Integration Detection), a novel experimental and computational method to detect the location of Hepatitis B Virus (HBV) integration breakpoints in Hepatocellular Carcinoma (HCC) genome. In this method, the fragments with HBV sequence were enriched by a set of HBV probes and then processed to high-throughput sequencing. In order to evaluate the performance of HIVID, we compared the results of HIVID with that of whole genome sequencing method (WGS) in 28 HCC tumors. We detected a total of 246 HBV integration breakpoints in HCC genome, 113 out of which were within 400bp upstream or downstream of 125 breakpoints identified by WGS method, covering 89.3% (125/140) of total breakpoints. The integration was located in the gene TERT, MLL4, and CCNE1. In addition, we discovered 133 novel breakpoints missed by WGS method, with 66.7% (10/15) of validation rate. Our study shows HIVID is a cost-effective methodology with high specificity and sensitivity to identify viral integration in human genome.
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China; School of Bioscience and Bioengineering, South China University of Technology, China.
authors.forename: Weiyang
authors.initials: W
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Zeng
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Shengpei
authors.initials: S
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Guo
authors.forename: Shang
authors.initials: S
authors.lastname: Yi
authors.forename: Xuehan
authors.initials: X
authors.lastname: Zhuang
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Ronnie T
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.lastname: Jianwang
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D002681:China; D019927:Cyclin E / Q000235:genetics; D053960:DNA Breaks; D004268:DNA-Binding Proteins / Q000235:genetics; D015894:Genome, Human; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000191:economics / Q000379:methods*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D015513:Oncogene Proteins / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D016662:Virus Integration
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; D011495:Histone-Lysine N-Methyltransferase; C530816:MLL4 protein, human; C509186:TERT protein, human; D019098:Telomerase
keywords: Capture; Cost-effective; Hepatocellular carcinoma; High-throughput; Integration