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SegCorr a statistical procedure for the detection of genomic regions of correlated expression

BACKGROUND: Detecting local correlations in expression between neighboring genes along the genome has proved to be an effective strategy to identify possible causes of transcriptional deregulation in cancer. It has been successfully used to illustrate the role of mechanisms such as copy number varia...

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Autores principales: Delatola, Eleni Ioanna, Lebarbier, Emilie, Mary-Huard, Tristan, Radvanyi, François, Robin, Stéphane, Wong, Jennifer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504623/
https://www.ncbi.nlm.nih.gov/pubmed/28697800
http://dx.doi.org/10.1186/s12859-017-1742-5
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author Delatola, Eleni Ioanna
Lebarbier, Emilie
Mary-Huard, Tristan
Radvanyi, François
Robin, Stéphane
Wong, Jennifer
author_facet Delatola, Eleni Ioanna
Lebarbier, Emilie
Mary-Huard, Tristan
Radvanyi, François
Robin, Stéphane
Wong, Jennifer
author_sort Delatola, Eleni Ioanna
collection PubMed
description BACKGROUND: Detecting local correlations in expression between neighboring genes along the genome has proved to be an effective strategy to identify possible causes of transcriptional deregulation in cancer. It has been successfully used to illustrate the role of mechanisms such as copy number variation (CNV) or epigenetic alterations as factors that may significantly alter expression in large chromosomal regions (gene silencing or gene activation). RESULTS: The identification of correlated regions requires segmenting the gene expression correlation matrix into regions of homogeneously correlated genes and assessing whether the observed local correlation is significantly higher than the background chromosomal correlation. A unified statistical framework is proposed to achieve these two tasks, where optimal segmentation is efficiently performed using dynamic programming algorithm, and detection of highly correlated regions is then achieved using an exact test procedure. We also propose a simple and efficient procedure to correct the expression signal for mechanisms already known to impact expression correlation. The performance and robustness of the proposed procedure, called SegCorr, are evaluated on simulated data. The procedure is illustrated on cancer data, where the signal is corrected for correlations caused by copy number variation. It permitted the detection of regions with high correlations linked to epigenetic marks like DNA methylation. CONCLUSIONS: SegCorr is a novel method that performs correlation matrix segmentation and applies a test procedure in order to detect highly correlated regions in gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1742-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-55046232017-07-12 SegCorr a statistical procedure for the detection of genomic regions of correlated expression Delatola, Eleni Ioanna Lebarbier, Emilie Mary-Huard, Tristan Radvanyi, François Robin, Stéphane Wong, Jennifer BMC Bioinformatics Methodology Article BACKGROUND: Detecting local correlations in expression between neighboring genes along the genome has proved to be an effective strategy to identify possible causes of transcriptional deregulation in cancer. It has been successfully used to illustrate the role of mechanisms such as copy number variation (CNV) or epigenetic alterations as factors that may significantly alter expression in large chromosomal regions (gene silencing or gene activation). RESULTS: The identification of correlated regions requires segmenting the gene expression correlation matrix into regions of homogeneously correlated genes and assessing whether the observed local correlation is significantly higher than the background chromosomal correlation. A unified statistical framework is proposed to achieve these two tasks, where optimal segmentation is efficiently performed using dynamic programming algorithm, and detection of highly correlated regions is then achieved using an exact test procedure. We also propose a simple and efficient procedure to correct the expression signal for mechanisms already known to impact expression correlation. The performance and robustness of the proposed procedure, called SegCorr, are evaluated on simulated data. The procedure is illustrated on cancer data, where the signal is corrected for correlations caused by copy number variation. It permitted the detection of regions with high correlations linked to epigenetic marks like DNA methylation. CONCLUSIONS: SegCorr is a novel method that performs correlation matrix segmentation and applies a test procedure in order to detect highly correlated regions in gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1742-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-11 /pmc/articles/PMC5504623/ /pubmed/28697800 http://dx.doi.org/10.1186/s12859-017-1742-5 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Delatola, Eleni Ioanna
Lebarbier, Emilie
Mary-Huard, Tristan
Radvanyi, François
Robin, Stéphane
Wong, Jennifer
SegCorr a statistical procedure for the detection of genomic regions of correlated expression
title SegCorr a statistical procedure for the detection of genomic regions of correlated expression
title_full SegCorr a statistical procedure for the detection of genomic regions of correlated expression
title_fullStr SegCorr a statistical procedure for the detection of genomic regions of correlated expression
title_full_unstemmed SegCorr a statistical procedure for the detection of genomic regions of correlated expression
title_short SegCorr a statistical procedure for the detection of genomic regions of correlated expression
title_sort segcorr a statistical procedure for the detection of genomic regions of correlated expression
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504623/
https://www.ncbi.nlm.nih.gov/pubmed/28697800
http://dx.doi.org/10.1186/s12859-017-1742-5
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