Evidence map›Paper›PMID 24721906›Full record

ArticlePLoS genetics2014

Chromatin landscapes of retroviral and transposon integration profiles.

Johann de Jong, Waseem Akhtar, Jitendra Badhai, Alistair G Rust, Roland Rad, John Hilkens, Anton Berns, Maarten van Lohuizen, Lodewyk F A Wessels, Jeroen de Ridder

Abstract read
In one paragraph

Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing 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

60 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  6. Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  7. Review
  8. Article
  9. International journal of molecular sciences · 2023
    Article
  10. Article
  11. Review
  12. Article
  13. Cell genomics · 2023
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Jumping Ahead withViruses · 2021
    Review
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

10 authors.

Johann de JongComputational Cancer Biology Group, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands.
Waseem AkhtarNetherlands Consortium for Systems Biology, Amsterdam, The Netherlands; Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jitendra BadhaiDivision of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Alistair G RustWellcome Trust Sanger Institute, Genome Campus, Hinxton-Cambridge, United Kingdom.
Roland RadDepartment of Medicine II; Klinikum Rechts der Isar; Technische Universität München, German Cancer Research Center (DKFZ), Heidelberg, & German Cancer Consortium (DKTK), Heidelberg, Germany.
John HilkensDivision of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Anton BernsDivision of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Skoltech Center for Stem Cell Research, Skolkovo Institute for Science and Technology, Skolkovo, Odintsovsky, Moscow, Russia.
Maarten van LohuizenNetherlands Consortium for Systems Biology, Amsterdam, The Netherlands; Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Lodewyk F A WesselsComputational Cancer Biology Group, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands; Delft Bioinformatics Lab, Faculty of EEMCS, TU Delft, Delft, The Netherlands.
Jeroen de RidderDelft Bioinformatics Lab, Faculty of EEMCS, TU Delft, Delft, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of ~ 120,000 to ~ 180,000 unselected integrations in the mouse genome for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary Tumor Virus (MMTV). We analyzed ~ 80 (epi)genomic features to generate bias maps at both local and genome-wide scales. MMTV showed a remarkably uniform distribution of integrations across the genome. More distinct preferences were observed for the two transposons, with PB showing remarkable resemblance to bias profiles of the Murine Leukemia Virus. Furthermore, we present a model where target site selection is directed at multiple scales. At a large scale, target site selection is similar across systems, and defined by domain-oriented features, namely expression of proximal genes, proximity to CpG islands and to genic features, chromatin compaction and replication timing. Notable differences between the systems are mainly observed at smaller scales, and are directed by a diverse range of features. To study the effect of these biases on integration sites occupied under selective pressure, we turned to insertional mutagenesis (IM) screens. In IM screens, putative cancer genes are identified by finding frequently targeted genomic regions, or Common Integration Sites (CISs). Within three recently completed IM screens, we identified 7%-33% putative false positive CISs, which are likely not the result of the oncogenic selection process. Moreover, results indicate that PB, compared to SB, is more suited to tag oncogenes.

Indexed as

AnimalsChromatinCpG IslandsDNA Transposable ElementsGenomeMiceMutagenesis, InsertionalOncogenesRetroviridaeChromatinDNA Transposable Elements

Identifiers

PMID24721906
PMCPMC3983033

What OpenQuestion holds

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Registered trials

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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.