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

Overview of attention for article published in Molecular Therapy - Methods & Clinical Development, December 2016
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1 patent

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165 Mendeley
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Title
INSPIIRED: A Pipeline for Quantitative Analysis of Sites of New DNA Integration in Cellular Genomes
Published in
Molecular Therapy - Methods & Clinical Development, December 2016
DOI 10.1016/j.omtm.2016.11.002
Pubmed ID
Authors

Eric Sherman, Christopher Nobles, Charles C. Berry, Emmanuelle Six, Yinghua Wu, Anatoly Dryga, Nirav Malani, Frances Male, Shantan Reddy, Aubrey Bailey, Kyle Bittinger, John K. Everett, Laure Caccavelli, Mary J. Drake, Paul Bates, Salima Hacein-Bey-Abina, Marina Cavazzana, Frederic D. Bushman

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.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 165 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Unknown 164 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 38 23%
Student > Ph. D. Student 25 15%
Student > Bachelor 14 8%
Student > Master 12 7%
Student > Doctoral Student 9 5%
Other 22 13%
Unknown 45 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 40 24%
Agricultural and Biological Sciences 25 15%
Immunology and Microbiology 14 8%
Medicine and Dentistry 11 7%
Engineering 7 4%
Other 20 12%
Unknown 48 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 December 2023.
All research outputs
#8,618,954
of 25,584,565 outputs
Outputs from Molecular Therapy - Methods & Clinical Development
#644
of 1,200 outputs
Outputs of similar age
#145,289
of 423,806 outputs
Outputs of similar age from Molecular Therapy - Methods & Clinical Development
#20
of 33 outputs
Altmetric has tracked 25,584,565 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,200 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.0. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 423,806 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.