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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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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. |
format | Online Article Text |
id | pubmed-7703754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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