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...
Main Authors: | , , , , , , , |
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Format: | Article |
Language: | English |
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BMC
2017-08-01
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Series: | Genome Medicine |
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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 . |
first_indexed | 2024-12-13T08:26:35Z |
format | Article |
id | doaj.art-16a8687e5b1941109d124dadcf0669a0 |
institution | Directory Open Access Journal |
issn | 1756-994X |
language | English |
last_indexed | 2024-12-13T08:26:35Z |
publishDate | 2017-08-01 |
publisher | BMC |
record_format | Article |
series | Genome Medicine |
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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