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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Main Authors:	Tamborero, David, Lopez-Bigas, Nuria, Gonzalez-Perez, Abel
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568145/

id	pubmed-3568145
recordtype	oai_dc
spelling	pubmed-35681452013-02-13 Oncodrive-CIS: A Method to Reveal Likely Driver Genes Based on the Impact of Their Copy Number Changes on Expression Tamborero, David Lopez-Bigas, Nuria Gonzalez-Perez, Abel Research Article 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. Public Library of Science 2013-02-08 /pmc/articles/PMC3568145/ /pubmed/23408991 http://dx.doi.org/10.1371/journal.pone.0055489 Text en © 2013 Tamborero et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Tamborero, David Lopez-Bigas, Nuria Gonzalez-Perez, Abel
spellingShingle	Tamborero, David Lopez-Bigas, Nuria Gonzalez-Perez, Abel Oncodrive-CIS: A Method to Reveal Likely Driver Genes Based on the Impact of Their Copy Number Changes on Expression
author_facet	Tamborero, David Lopez-Bigas, Nuria Gonzalez-Perez, Abel
author_sort	Tamborero, David
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
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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568145/
_version_	1611953644342607872

Oncodrive-CIS: A Method to Reveal Likely Driver Genes Based on the Impact of Their Copy Number Changes on Expression

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