Retroviral integration process in the human genome: is it really non-random? A new statistical approach.

Retroviral vectors are widely used in gene therapy to introduce therapeutic genes into patients' cells, since, once delivered to the nucleus, the genes of interest are stably inserted (integrated) into the target cell genome. There is now compelling evidence that integration of retroviral vecto...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alessandro Ambrosi, Claudia Cattoglio, Clelia Di Serio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/32885fd82f4c4bf999db311917c21d85
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:32885fd82f4c4bf999db311917c21d85
record_format	dspace
spelling	oai:doaj.org-article:32885fd82f4c4bf999db311917c21d852021-11-25T05:41:11ZRetroviral integration process in the human genome: is it really non-random? A new statistical approach.1553-734X1553-735810.1371/journal.pcbi.1000144https://doaj.org/article/32885fd82f4c4bf999db311917c21d852008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18688267/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Retroviral vectors are widely used in gene therapy to introduce therapeutic genes into patients' cells, since, once delivered to the nucleus, the genes of interest are stably inserted (integrated) into the target cell genome. There is now compelling evidence that integration of retroviral vectors follows non-random patterns in mammalian genome, with a preference for active genes and regulatory regions. In particular, Moloney Leukemia Virus (MLV)-derived vectors show a tendency to integrate in the proximity of the transcription start site (TSS) of genes, occasionally resulting in the deregulation of gene expression and, where proto-oncogenes are targeted, in tumor initiation. This has drawn the attention of the scientific community to the molecular determinants of the retroviral integration process as well as to statistical methods to evaluate the genome-wide distribution of integration sites. In recent approaches, the observed distribution of MLV integration distances (IDs) from the TSS of the nearest gene is assumed to be non-random by empirical comparison with a random distribution generated by computational simulation procedures. To provide a statistical procedure to test the randomness of the retroviral insertion pattern, we propose a probability model (Beta distribution) based on IDs between two consecutive genes. We apply the procedure to a set of 595 unique MLV insertion sites retrieved from human hematopoietic stem/progenitor cells. The statistical goodness of fit test shows the suitability of this distribution to the observed data. Our statistical analysis confirms the preference of MLV-based vectors to integrate in promoter-proximal regions.Alessandro AmbrosiClaudia CattoglioClelia Di SerioPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 8, p e1000144 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Alessandro Ambrosi Claudia Cattoglio Clelia Di Serio Retroviral integration process in the human genome: is it really non-random? A new statistical approach.
description	Retroviral vectors are widely used in gene therapy to introduce therapeutic genes into patients' cells, since, once delivered to the nucleus, the genes of interest are stably inserted (integrated) into the target cell genome. There is now compelling evidence that integration of retroviral vectors follows non-random patterns in mammalian genome, with a preference for active genes and regulatory regions. In particular, Moloney Leukemia Virus (MLV)-derived vectors show a tendency to integrate in the proximity of the transcription start site (TSS) of genes, occasionally resulting in the deregulation of gene expression and, where proto-oncogenes are targeted, in tumor initiation. This has drawn the attention of the scientific community to the molecular determinants of the retroviral integration process as well as to statistical methods to evaluate the genome-wide distribution of integration sites. In recent approaches, the observed distribution of MLV integration distances (IDs) from the TSS of the nearest gene is assumed to be non-random by empirical comparison with a random distribution generated by computational simulation procedures. To provide a statistical procedure to test the randomness of the retroviral insertion pattern, we propose a probability model (Beta distribution) based on IDs between two consecutive genes. We apply the procedure to a set of 595 unique MLV insertion sites retrieved from human hematopoietic stem/progenitor cells. The statistical goodness of fit test shows the suitability of this distribution to the observed data. Our statistical analysis confirms the preference of MLV-based vectors to integrate in promoter-proximal regions.
format	article
author	Alessandro Ambrosi Claudia Cattoglio Clelia Di Serio
author_facet	Alessandro Ambrosi Claudia Cattoglio Clelia Di Serio
author_sort	Alessandro Ambrosi
title	Retroviral integration process in the human genome: is it really non-random? A new statistical approach.
title_short	Retroviral integration process in the human genome: is it really non-random? A new statistical approach.
title_full	Retroviral integration process in the human genome: is it really non-random? A new statistical approach.
title_fullStr	Retroviral integration process in the human genome: is it really non-random? A new statistical approach.
title_full_unstemmed	Retroviral integration process in the human genome: is it really non-random? A new statistical approach.
title_sort	retroviral integration process in the human genome: is it really non-random? a new statistical approach.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/32885fd82f4c4bf999db311917c21d85
work_keys_str_mv	AT alessandroambrosi retroviralintegrationprocessinthehumangenomeisitreallynonrandomanewstatisticalapproach AT claudiacattoglio retroviralintegrationprocessinthehumangenomeisitreallynonrandomanewstatisticalapproach AT cleliadiserio retroviralintegrationprocessinthehumangenomeisitreallynonrandomanewstatisticalapproach
_version_	1718414510540193792

Retroviral integration process in the human genome: is it really non-random? A new statistical approach.

Ejemplares similares