Evidence map›Paper›PMID 34287049›Full record

ArticleJournal of virology2021

Targeted Long-Read Sequencing Reveals Comprehensive Architecture, Burden, and Transcriptional Signatures from Hepatitis B Virus-Associated Integrations and Translocations in Hepatocellular Carcinoma Cell Lines.

Ricardo Ramirez, Nicholas van Buuren, Lindsay Gamelin, Cameron Soulette, Lindsey May, Dong Han, Mei Yu, Regina Choy, Guofeng Cheng, Neeru Bhardwaj and 6 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 49 citations in OpenAlex.

  1. Trial
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  9. Article
  10. HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  11. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Ricardo Ramirez *Gilead Sciences Inc., Foster City, California, USA.
Nicholas van Buuren *Gilead Sciences Inc., Foster City, California, USA.
Lindsay Gamelin *Gilead Sciences Inc., Foster City, California, USA.
Cameron SouletteGilead Sciences Inc., Foster City, California, USA.
Lindsey MayGilead Sciences Inc., Foster City, California, USA.
Dong HanGilead Sciences Inc., Foster City, California, USA.
Mei YuGilead Sciences Inc., Foster City, California, USA.
Regina ChoyGilead Sciences Inc., Foster City, California, USA.
Guofeng ChengGilead Sciences Inc., Foster City, California, USA.
Neeru BhardwajGilead Sciences Inc., Foster City, California, USA.
Joy ChiuGilead Sciences Inc., Foster City, California, USA.
Robert C MuenchGilead Sciences Inc., Foster City, California, USA.
William E DelaneyGilead Sciences Inc., Foster City, California, USA.
Hongmei MoGilead Sciences Inc., Foster City, California, USA.
Becket FeierbachGilead Sciences Inc., Foster City, California, USA.
Li LiGilead Sciences Inc., Foster City, California, USA.ORCID 0000-0002-7171-6271
Gilead Sciences (United States) · US

Funding

Gilead Sciences (Gilead)
6 · The paper itself

Abstract

Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, creating potentially oncogenic lesions that can lead to hepatocellular carcinoma (HCC). However, our current understanding of integrated HBV DNA architecture, burden, and transcriptional activity is incomplete due to technical limitations. A combination of genomics approaches was used to describe HBV integrations and corresponding transcriptional signatures in three HCC cell lines: huH-1, PLC/PRF/5, and Hep3B. To generate high-coverage, long-read sequencing data, a custom panel of HBV-targeting biotinylated oligonucleotide probes was designed. Targeted long-read DNA sequencing captured entire HBV integration events within individual reads, revealing that integrations may include deletions and inversions of viral sequences. Surprisingly, all three HCC cell lines contain integrations that are associated with host chromosomal translocations. In addition, targeted long-read RNA sequencing allowed for the assignment of transcriptional activity to specific integrations and resolved the contribution of overlapping HBV transcripts. HBV transcripts chimeric with host sequences were resolved in their entirety and often included >1,000 bp of host sequence. This study provides the first comprehensive description of HBV integrations and associated transcriptional activity in three commonly utilized HCC-derived cell lines. The application of novel methods sheds new light on the complexity of these integrations, including HBV bidirectional transcription, nested transcripts, silent integrations, and host genomic rearrangements. The observation of multiple HBV-associated chromosomal translocations gives rise to the hypothesis that HBV is a driver of genetic instability and provides a potential new mechanism for HCC development.

Indexed as

Cell Line, TumorTranscription, GeneticTranslocation, GeneticVirus IntegrationCarcinoma, HepatocellularDNA, ViralHepatitis B virusHumansSequence Analysis, DNASequence Analysis, RNADNA, Viralchromosomal translocationHBVHCCviral integration

Identifiers

PMID34287049
PMCPMC8428387
OpenAlexW3185401483

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.