Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.

Integration of retroviral vectors in the human genome follows non random patterns that favor insertional deregulation of gene expression and may cause risks of insertional mutagenesis when used in clinical gene therapy. Understanding how viral vectors integrate into the human genome is a key issue i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alessandro Ambrosi, Ingrid K Glad, Danilo Pellin, Claudia Cattoglio, Fulvio Mavilio, Clelia Di Serio, Arnoldo Frigessi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b748488d5f6645e5b180f89676e39bf3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b748488d5f6645e5b180f89676e39bf3
record_format	dspace
spelling	oai:doaj.org-article:b748488d5f6645e5b180f89676e39bf32021-11-18T05:51:44ZEstimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.1553-734X1553-735810.1371/journal.pcbi.1002292https://doaj.org/article/b748488d5f6645e5b180f89676e39bf32011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22144885/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Integration of retroviral vectors in the human genome follows non random patterns that favor insertional deregulation of gene expression and may cause risks of insertional mutagenesis when used in clinical gene therapy. Understanding how viral vectors integrate into the human genome is a key issue in predicting these risks. We provide a new statistical method to compare retroviral integration patterns. We identified the positions where vectors derived from the Human Immunodeficiency Virus (HIV) and the Moloney Murine Leukemia Virus (MLV) show different integration behaviors in human hematopoietic progenitor cells. Non-parametric density estimation was used to identify candidate comparative hotspots, which were then tested and ranked. We found 100 significative comparative hotspots, distributed throughout the chromosomes. HIV hotspots were wider and contained more genes than MLV ones. A Gene Ontology analysis of HIV targets showed enrichment of genes involved in antigen processing and presentation, reflecting the high HIV integration frequency observed at the MHC locus on chromosome 6. Four histone modifications/variants had a different mean density in comparative hotspots (H2AZ, H3K4me1, H3K4me3, H3K9me1), while gene expression within the comparative hotspots did not differ from background. These findings suggest the existence of epigenetic or nuclear three-dimensional topology contexts guiding retroviral integration to specific chromosome areas.Alessandro AmbrosiIngrid K GladDanilo PellinClaudia CattoglioFulvio MavilioClelia Di SerioArnoldo FrigessiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 12, p e1002292 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Alessandro Ambrosi Ingrid K Glad Danilo Pellin Claudia Cattoglio Fulvio Mavilio Clelia Di Serio Arnoldo Frigessi Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
description	Integration of retroviral vectors in the human genome follows non random patterns that favor insertional deregulation of gene expression and may cause risks of insertional mutagenesis when used in clinical gene therapy. Understanding how viral vectors integrate into the human genome is a key issue in predicting these risks. We provide a new statistical method to compare retroviral integration patterns. We identified the positions where vectors derived from the Human Immunodeficiency Virus (HIV) and the Moloney Murine Leukemia Virus (MLV) show different integration behaviors in human hematopoietic progenitor cells. Non-parametric density estimation was used to identify candidate comparative hotspots, which were then tested and ranked. We found 100 significative comparative hotspots, distributed throughout the chromosomes. HIV hotspots were wider and contained more genes than MLV ones. A Gene Ontology analysis of HIV targets showed enrichment of genes involved in antigen processing and presentation, reflecting the high HIV integration frequency observed at the MHC locus on chromosome 6. Four histone modifications/variants had a different mean density in comparative hotspots (H2AZ, H3K4me1, H3K4me3, H3K9me1), while gene expression within the comparative hotspots did not differ from background. These findings suggest the existence of epigenetic or nuclear three-dimensional topology contexts guiding retroviral integration to specific chromosome areas.
format	article
author	Alessandro Ambrosi Ingrid K Glad Danilo Pellin Claudia Cattoglio Fulvio Mavilio Clelia Di Serio Arnoldo Frigessi
author_facet	Alessandro Ambrosi Ingrid K Glad Danilo Pellin Claudia Cattoglio Fulvio Mavilio Clelia Di Serio Arnoldo Frigessi
author_sort	Alessandro Ambrosi
title	Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
title_short	Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
title_full	Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
title_fullStr	Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
title_full_unstemmed	Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
title_sort	estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b748488d5f6645e5b180f89676e39bf3
work_keys_str_mv	AT alessandroambrosi estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors AT ingridkglad estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors AT danilopellin estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors AT claudiacattoglio estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors AT fulviomavilio estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors AT cleliadiserio estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors AT arnoldofrigessi estimatedcomparativeintegrationhotspotsidentifydifferentbehaviorsofretroviralgenetransfervectors
_version_	1718424751147319296

Estimated comparative integration hotspots identify different behaviors of retroviral gene transfer vectors.

Ejemplares similares