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γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites

SUMMARY: Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene the...

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Autores principales: Calabria, Andrea, Beretta, Stefano, Merelli, Ivan, Spinozzi, Giulio, Brasca, Stefano, Pirola, Yuri, Benedicenti, Fabrizio, Tenderini, Erika, Bonizzoni, Paola, Milanesi, Luciano, Montini, Eugenio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703754/
https://www.ncbi.nlm.nih.gov/pubmed/31589304
http://dx.doi.org/10.1093/bioinformatics/btz747
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author Calabria, Andrea
Beretta, Stefano
Merelli, Ivan
Spinozzi, Giulio
Brasca, Stefano
Pirola, Yuri
Benedicenti, Fabrizio
Tenderini, Erika
Bonizzoni, Paola
Milanesi, Luciano
Montini, Eugenio
author_facet Calabria, Andrea
Beretta, Stefano
Merelli, Ivan
Spinozzi, Giulio
Brasca, Stefano
Pirola, Yuri
Benedicenti, Fabrizio
Tenderini, Erika
Bonizzoni, Paola
Milanesi, Luciano
Montini, Eugenio
author_sort Calabria, Andrea
collection PubMed
description SUMMARY: Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene therapy or virally infected patients, essential for monitoring the evolution of genetically modified cells in vivo. However, since ∼30% of insertions land in low complexity or repetitive regions of the host cell genome, they cannot be correctly assigned and are currently discarded, limiting the accuracy and predictive power of clonal tracking studies. Here, we present γ-TRIS, a new graph-based genome-free alignment tool for identifying insertion sites even if embedded in low complexity regions. By using γ-TRIS to reanalyze clinical studies, we observed improvements in clonal quantification and tracking. AVAILABILITY AND IMPLEMENTATION: Source code at https://bitbucket.org/bereste/g-tris. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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spelling pubmed-77037542020-12-07 γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites Calabria, Andrea Beretta, Stefano Merelli, Ivan Spinozzi, Giulio Brasca, Stefano Pirola, Yuri Benedicenti, Fabrizio Tenderini, Erika Bonizzoni, Paola Milanesi, Luciano Montini, Eugenio Bioinformatics Applications Note SUMMARY: Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene therapy or virally infected patients, essential for monitoring the evolution of genetically modified cells in vivo. However, since ∼30% of insertions land in low complexity or repetitive regions of the host cell genome, they cannot be correctly assigned and are currently discarded, limiting the accuracy and predictive power of clonal tracking studies. Here, we present γ-TRIS, a new graph-based genome-free alignment tool for identifying insertion sites even if embedded in low complexity regions. By using γ-TRIS to reanalyze clinical studies, we observed improvements in clonal quantification and tracking. AVAILABILITY AND IMPLEMENTATION: Source code at https://bitbucket.org/bereste/g-tris. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Oxford University Press 2020-03 2019-10-07 /pmc/articles/PMC7703754/ /pubmed/31589304 http://dx.doi.org/10.1093/bioinformatics/btz747 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Applications Note
Calabria, Andrea
Beretta, Stefano
Merelli, Ivan
Spinozzi, Giulio
Brasca, Stefano
Pirola, Yuri
Benedicenti, Fabrizio
Tenderini, Erika
Bonizzoni, Paola
Milanesi, Luciano
Montini, Eugenio
γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites
title γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites
title_full γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites
title_fullStr γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites
title_full_unstemmed γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites
title_short γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites
title_sort γ-tris: a graph-algorithm for comprehensive identification of vector genomic insertion sites
topic Applications Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703754/
https://www.ncbi.nlm.nih.gov/pubmed/31589304
http://dx.doi.org/10.1093/bioinformatics/btz747
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