Evidence map›Paper›PMID 28344990›Full record

ArticleMolecular therapy. Methods & clinical development2017

INSPIIRED: A Pipeline for Quantitative Analysis of Sites of New DNA Integration in Cellular Genomes.

Eric Sherman, Christopher Nobles, Charles C Berry, Emmanuelle Six, Yinghua Wu, Anatoly Dryga, Nirav Malani, Frances Male, Shantan Reddy, Aubrey Bailey and 8 more

Abstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing 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

98 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

38 more citing papers are in PubMed but not listed here.

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

18 authors.

Eric ShermanDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Christopher NoblesDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Charles C BerryDepartment of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA 92093, USA.
Emmanuelle SixImagine Institute, Paris Descartes-Sorbonne Paris Cité University, 75014 Paris, France; Laboratory of Human Lymphohematopoiesis, INSERM 24, 75014 Paris, France.
Yinghua WuDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Anatoly DrygaDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Nirav MalaniDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Frances MaleDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Shantan ReddyDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Aubrey BaileyDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Kyle BittingerDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
John K EverettDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Laure CaccavelliBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, 75014 Paris, France.
Mary J DrakeDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Paul BatesDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
Salima Hacein-Bey-AbinaBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, 75014 Paris, France.
Marina CavazzanaBiotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpitaux de Paris, INSERM, 75014 Paris, France.
Frederic D BushmanDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Sequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2015 to 2019
$12.0M
Role of co-receptor modified cells in HIV infectionU01AI104400 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2013 to 2016
$5.8M
Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
Massively Parallel Analysis of Integration in Therapeutic Gene TransferR01AI082020 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2009 to 2018
$3.5M
Lung Transplant Microbiome and Chronic Allograft DysfunctionR01HL113252 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D, CHRISTIE, JASON D · 2013 to 2016
$2.9M
Role of co-receptor modified cells in HIV infectionR01AI104400 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2012 to 2012
$1.3M
European Research Council 269037NHLBI NIH HHS R01 HL113252NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI052845NIAID NIH HHS R01 AI082020NIAID NIH HHS R01 AI104400NIAID NIH HHS U01 AI104400NIAID NIH HHS U19 AI117950
6 · The paper itself

Abstract

Integration of new DNA into cellular genomes mediates replication of retroviruses and transposons; integration reactions have also been adapted for use in human gene therapy. Tracking the distributions of integration sites is important to characterize populations of transduced cells and to monitor potential outgrow of pathogenic cell clones. Here, we describe a pipeline for quantitative analysis of integration site distributions named INSPIIRED (integration site pipeline for paired-end reads). We describe optimized biochemical steps for site isolation using Illumina paired-end sequencing, including new technology for suppressing recovery of unwanted contaminants, then software for alignment, quality control, and management of integration site sequences. During library preparation, DNAs are broken by sonication, so that after ligation-mediated PCR the number of ligation junction sites can be used to infer abundance of gene-modified cells. We generated integration sites of known positions in silico, and we describe optimization of sample processing parameters refined by comparison to truth. We also present a novel graph-theory-based method for quantifying integration sites in repeated sequences, and we characterize the consequences using synthetic and experimental data. In an accompanying paper, we describe an additional set of statistical tools for data analysis and visualization. Software is available at https://github.com/BushmanLab/INSPIIRED.

Indexed as

gammaretrovirusgene therapyinsertional mutagenesislentivirusmutagenesisrecombinationretrovirusSCID-X1vectorvector driving

Identifiers

PMID28344990
PMCPMC5363316

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.