Evidence map›Paper›PMID 23720718›Full record

ArticleJournal of virology2013

High-throughput sequencing reveals principles of adeno-associated virus serotype 2 integration.

Tyler Janovitz, Isaac A Klein, Thiago Oliveira, Piali Mukherjee, Michel C Nussenzweig, Michel Sadelain, Erik Falck-Pedersen

Abstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Article
  2. Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023
    Review
  3. Article
  4. Article
  5. Adeno-associated virus Rep proteins antagonize phosphatase PP1 to counteract KAP1 repression of the latent viral genome.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  6. LinearPeerJ · 2018
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

7 authors.

Tyler JanovitzTri-Institutional MD-PhD Program, Weill Medical College of Cornell University, New York, New York, USA.
Isaac A Klein
Thiago Oliveira
Piali Mukherjee
Michel C Nussenzweig
Michel Sadelain
Erik Falck-Pedersen

Funding

Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
Class Switch Recombination in B LymphocytesR37AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2014 to 2023
$5.4M
SIGNALLING PATHWAYS IN AUTOIMMUNITYR01AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 1994 to 2012
$5.0M
Regulation of host cell inflammatory and maturation response through AdV DNAdeteR01AI094050 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI FALCK-PEDERSEN, ERIK S · 2011 to 2015
$2.1M
Howard Hughes Medical InstituteNIAID NIH HHS AI037526NIAID NIH HHS R01 AI037526NIAID NIH HHS R01 AI094050NIAID NIH HHS R37 AI037526NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32GM07739
6 · The paper itself

Abstract

Viral integrations are important in human biology, yet genome-wide integration profiles have not been determined for many viruses. Adeno-associated virus (AAV) infects most of the human population and is a prevalent gene therapy vector. AAV integrates into the human genome with preference for a single locus, termed AAVS1. However, the genome-wide integration of AAV has not been defined, and the principles underlying this recombination remain unclear. Using a novel high-throughput approach, integrant capture sequencing, nearly 12 million AAV junctions were recovered from a human cell line, providing five orders of magnitude more data than were previously available. Forty-five percent of integrations occurred near AAVS1, and several thousand novel integration hotspots were identified computationally. Most of these occurred in genes, with dozens of hotspots targeting known oncogenes. Viral replication protein binding sites (RBS) and transcriptional activity were major factors favoring integration. In a first for eukaryotic viruses, the data reveal a unique asymmetric integration profile with distinctive directional orientation of viral genomes. These studies provide a new understanding of AAV integration biology through the use of unbiased high-throughput data acquisition and bioinformatics.

Indexed as

Virus IntegrationDependovirusGenome, HumanGenome, ViralHeLa CellsHigh-Throughput Nucleotide SequencingHumansRecombination, Genetic

Identifiers

PMID23720718
PMCPMC3719808

What OpenQuestion holds

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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.