Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.

A well-established approach for detecting genes involved in tumorigenesis due to copy number alterations (CNAs) is to assess the recurrence of the alteration across multiple samples. Expression data can be used to filter this list of candidates by assessing whether the gene expression significantly...

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Autores principales:	David Tamborero, Nuria Lopez-Bigas, Abel Gonzalez-Perez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4acf915e62d54827a7558fb8a2cb02fe
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spelling	oai:doaj.org-article:4acf915e62d54827a7558fb8a2cb02fe2021-11-18T07:58:11ZOncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.1932-620310.1371/journal.pone.0055489https://doaj.org/article/4acf915e62d54827a7558fb8a2cb02fe2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23408991/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A well-established approach for detecting genes involved in tumorigenesis due to copy number alterations (CNAs) is to assess the recurrence of the alteration across multiple samples. Expression data can be used to filter this list of candidates by assessing whether the gene expression significantly differs between tumors depending on the copy number status. A drawback of this approach is that it may fail to detect low-recurrent drivers. Furthermore, this analysis does not provide information about expression changes for each gene as compared to the whole data set and does not take into consideration the expression of normal samples. Here we describe a novel method (Oncodrive-CIS) aimed at ranking genes according to the expression impact caused by the CNAs. The rationale of Oncodrive-CIS is based on the hypothesis that genes involved in cancer due to copy number changes are more biased towards misregulation than are bystanders. Moreover, to gain insight into the expression changes caused by gene dosage, the expression of samples with CNAs is compared to that of tumor samples with diploid genotype and also to that of normal samples. Oncodrive-CIS demonstrated better performance in detecting putative associations between copy-number and expression in simulated data sets as compared to other methods aimed to this purpose, and picked up genes likely to be related with tumorigenesis when applied to real cancer samples. In summary, Oncodrive-CIS provides a statistical framework to evaluate the in cis effect of CNAs that may be useful to elucidate the role of these aberrations in driving oncogenesis. An implementation of this method and the corresponding user guide are freely available at http://bg.upf.edu/oncodrivecis.David TamboreroNuria Lopez-BigasAbel Gonzalez-PerezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55489 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Tamborero Nuria Lopez-Bigas Abel Gonzalez-Perez Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
description	A well-established approach for detecting genes involved in tumorigenesis due to copy number alterations (CNAs) is to assess the recurrence of the alteration across multiple samples. Expression data can be used to filter this list of candidates by assessing whether the gene expression significantly differs between tumors depending on the copy number status. A drawback of this approach is that it may fail to detect low-recurrent drivers. Furthermore, this analysis does not provide information about expression changes for each gene as compared to the whole data set and does not take into consideration the expression of normal samples. Here we describe a novel method (Oncodrive-CIS) aimed at ranking genes according to the expression impact caused by the CNAs. The rationale of Oncodrive-CIS is based on the hypothesis that genes involved in cancer due to copy number changes are more biased towards misregulation than are bystanders. Moreover, to gain insight into the expression changes caused by gene dosage, the expression of samples with CNAs is compared to that of tumor samples with diploid genotype and also to that of normal samples. Oncodrive-CIS demonstrated better performance in detecting putative associations between copy-number and expression in simulated data sets as compared to other methods aimed to this purpose, and picked up genes likely to be related with tumorigenesis when applied to real cancer samples. In summary, Oncodrive-CIS provides a statistical framework to evaluate the in cis effect of CNAs that may be useful to elucidate the role of these aberrations in driving oncogenesis. An implementation of this method and the corresponding user guide are freely available at http://bg.upf.edu/oncodrivecis.
format	article
author	David Tamborero Nuria Lopez-Bigas Abel Gonzalez-Perez
author_facet	David Tamborero Nuria Lopez-Bigas Abel Gonzalez-Perez
author_sort	David Tamborero
title	Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
title_short	Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
title_full	Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
title_fullStr	Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
title_full_unstemmed	Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
title_sort	oncodrive-cis: a method to reveal likely driver genes based on the impact of their copy number changes on expression.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4acf915e62d54827a7558fb8a2cb02fe
work_keys_str_mv	AT davidtamborero oncodrivecisamethodtoreveallikelydrivergenesbasedontheimpactoftheircopynumberchangesonexpression AT nurialopezbigas oncodrivecisamethodtoreveallikelydrivergenesbasedontheimpactoftheircopynumberchangesonexpression AT abelgonzalezperez oncodrivecisamethodtoreveallikelydrivergenesbasedontheimpactoftheircopynumberchangesonexpression
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Oncodrive-CIS: a method to reveal likely driver genes based on the impact of their copy number changes on expression.

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