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INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions

Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED...

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Autores principales: Berry, Charles C., Nobles, Christopher, Six, Emmanuelle, Wu, Yinghua, Malani, Nirav, Sherman, Eric, Dryga, Anatoly, Everett, John K., Male, Frances, Bailey, Aubrey, Bittinger, Kyle, Drake, Mary J., Caccavelli, Laure, Bates, Paul, Hacein-Bey-Abina, Salima, Cavazzana, Marina, Bushman, Frederic D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363318/
https://www.ncbi.nlm.nih.gov/pubmed/28344988
http://dx.doi.org/10.1016/j.omtm.2016.11.003
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author Berry, Charles C.
Nobles, Christopher
Six, Emmanuelle
Wu, Yinghua
Malani, Nirav
Sherman, Eric
Dryga, Anatoly
Everett, John K.
Male, Frances
Bailey, Aubrey
Bittinger, Kyle
Drake, Mary J.
Caccavelli, Laure
Bates, Paul
Hacein-Bey-Abina, Salima
Cavazzana, Marina
Bushman, Frederic D.
author_facet Berry, Charles C.
Nobles, Christopher
Six, Emmanuelle
Wu, Yinghua
Malani, Nirav
Sherman, Eric
Dryga, Anatoly
Everett, John K.
Male, Frances
Bailey, Aubrey
Bittinger, Kyle
Drake, Mary J.
Caccavelli, Laure
Bates, Paul
Hacein-Bey-Abina, Salima
Cavazzana, Marina
Bushman, Frederic D.
author_sort Berry, Charles C.
collection PubMed
description Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50 (unique cell progenitors contributing the most expanded 50% of progeny cell clones), which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1 (SCID-X1), showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED.
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spelling pubmed-53633182017-03-24 INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions Berry, Charles C. Nobles, Christopher Six, Emmanuelle Wu, Yinghua Malani, Nirav Sherman, Eric Dryga, Anatoly Everett, John K. Male, Frances Bailey, Aubrey Bittinger, Kyle Drake, Mary J. Caccavelli, Laure Bates, Paul Hacein-Bey-Abina, Salima Cavazzana, Marina Bushman, Frederic D. Mol Ther Methods Clin Dev Original Article Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50 (unique cell progenitors contributing the most expanded 50% of progeny cell clones), which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1 (SCID-X1), showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. American Society of Gene & Cell Therapy 2016-12-18 /pmc/articles/PMC5363318/ /pubmed/28344988 http://dx.doi.org/10.1016/j.omtm.2016.11.003 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Berry, Charles C.
Nobles, Christopher
Six, Emmanuelle
Wu, Yinghua
Malani, Nirav
Sherman, Eric
Dryga, Anatoly
Everett, John K.
Male, Frances
Bailey, Aubrey
Bittinger, Kyle
Drake, Mary J.
Caccavelli, Laure
Bates, Paul
Hacein-Bey-Abina, Salima
Cavazzana, Marina
Bushman, Frederic D.
INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions
title INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions
title_full INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions
title_fullStr INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions
title_full_unstemmed INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions
title_short INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions
title_sort inspiired: quantification and visualization tools for analyzing integration site distributions
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363318/
https://www.ncbi.nlm.nih.gov/pubmed/28344988
http://dx.doi.org/10.1016/j.omtm.2016.11.003
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