Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks

Abstract The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying “personal” gene regulatory network. We validated μ-ci...

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Main Authors: Zeynep Kalender Atak, Hana Imrichova, Dmitry Svetlichnyy, Gert Hulselmans, Valerie Christiaens, Joke Reumers, Hugo Ceulemans, Stein Aerts
Format: Article
Language:English
Published: BMC 2017-08-01
Series:Genome Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13073-017-0464-7
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author Zeynep Kalender Atak
Hana Imrichova
Dmitry Svetlichnyy
Gert Hulselmans
Valerie Christiaens
Joke Reumers
Hugo Ceulemans
Stein Aerts
author_facet Zeynep Kalender Atak
Hana Imrichova
Dmitry Svetlichnyy
Gert Hulselmans
Valerie Christiaens
Joke Reumers
Hugo Ceulemans
Stein Aerts
author_sort Zeynep Kalender Atak
collection DOAJ
description Abstract The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying “personal” gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genomes of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers. μ-cisTarget is available from http://mucistarget.aertslab.org .
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spelling doaj.art-16a8687e5b1941109d124dadcf0669a02022-12-21T23:53:52ZengBMCGenome Medicine1756-994X2017-08-019111310.1186/s13073-017-0464-7Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networksZeynep Kalender Atak0Hana Imrichova1Dmitry Svetlichnyy2Gert Hulselmans3Valerie Christiaens4Joke Reumers5Hugo Ceulemans6Stein Aerts7Laboratory of Computational Biology, VIB Center for Brain & Disease ResearchLaboratory of Computational Biology, VIB Center for Brain & Disease ResearchLaboratory of Computational Biology, VIB Center for Brain & Disease ResearchLaboratory of Computational Biology, VIB Center for Brain & Disease ResearchLaboratory of Computational Biology, VIB Center for Brain & Disease ResearchDiscovery Sciences, Janssen Research & DevelopmentDiscovery Sciences, Janssen Research & DevelopmentLaboratory of Computational Biology, VIB Center for Brain & Disease ResearchAbstract The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying “personal” gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genomes of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers. μ-cisTarget is available from http://mucistarget.aertslab.org .http://link.springer.com/article/10.1186/s13073-017-0464-7cis-regulatory mutationsWhole-genome sequencingGene regulatory networksCancer genomics
spellingShingle Zeynep Kalender Atak
Hana Imrichova
Dmitry Svetlichnyy
Gert Hulselmans
Valerie Christiaens
Joke Reumers
Hugo Ceulemans
Stein Aerts
Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
Genome Medicine
cis-regulatory mutations
Whole-genome sequencing
Gene regulatory networks
Cancer genomics
title Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
title_full Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
title_fullStr Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
title_full_unstemmed Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
title_short Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
title_sort identification of cis regulatory mutations generating de novo edges in personalized cancer gene regulatory networks
topic cis-regulatory mutations
Whole-genome sequencing
Gene regulatory networks
Cancer genomics
url http://link.springer.com/article/10.1186/s13073-017-0464-7
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