Evidence map›Paper›PMID 29178837›Full record

ArticleBMC bioinformatics2017

VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.

Giulio Spinozzi, Andrea Calabria, Stefano Brasca, Stefano Beretta, Ivan Merelli, Luciano Milanesi, Eugenio Montini

Abstract read
In one paragraph

Article in BMC bioinformatics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Challenges in estimating numbers of vectors integrated in gene-modified cells using DNA sequence information.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    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.

Giulio SpinozziSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
Andrea CalabriaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
Stefano BrascaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
Stefano BerettaDepartment of Computer Science, University of Milano Bicocca, Viale Sarca, 336, 20126, Milan, Italy.
Ivan MerelliNational Research Council, Institute for Biomedical Technologies, Via Fratelli Cervi, 93, 20090, Segrate, Italy.
Luciano MilanesiNational Research Council, Institute for Biomedical Technologies, Via Fratelli Cervi, 93, 20090, Segrate, Italy.
Eugenio MontiniSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy. montini.eugenio@hsr.it.

Funding

Fondazione Telethon TGT11D1Fondazione Telethon TGT16B01Fondazione Telethon TGT16B03Italian Ministry of Education and Research through the Flagship InterOmics PB05Italian Super Computing Resource Allocation sponsored by CINECA for VISPA pipeline HP10CEUWXFUniversità degli Studi di Milano-Bicocca PhD Program
6 · The paper itself

Abstract

backgroundBioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time.

resultsHere we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free).

conclusionsWe tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).

Indexed as

User-Computer InterfaceAlgorithmsGenetic TherapyGenetic VectorsHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHigh-Throughput Nucleotide SequencingHumansLentivirusSequence AlignmentVirus InternalizationBioinformatics pipelineGene therapyHigh-throughput sequencingIntegration site analysisNext-generation sequencingOpen source softwareWorkflow

Identifiers

PMID29178837
PMCPMC5702242

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.