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

被引：11

作者：

Atak, Zeynep Kalender ^{[1
,2
]}

Imrichova, Hana ^{[1
,2
]}

Svetlichnyy, Dmitry ^{[1
,2
]}

Hulselmans, Gert ^{[1
,2
]}

Christiaens, Valerie ^{[1
,2
]}

Reumers, Joke ^{[3
]}

Ceulemans, Hugo ^{[3
]}

Aerts, Stein ^{[1
,2
]}

机构：

[1] VIB Ctr Brain & Dis Res, Lab Computat Biol, Leuven, Belgium

[2] Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium

[3] Janssen Res & Dev, Discovery Sci, Turnhoutseweg 30, B-2340 Beerse, Belgium

来源：

GENOME MEDICINE | 2017年 / 9卷

基金：

欧洲研究理事会; 比利时弗兰德研究基金会;

关键词：

cis-regulatory mutations; Whole-genome sequencing; Gene regulatory networks; Cancer genomics; ETS TRANSCRIPTION FACTORS; EPITHELIAL-MESENCHYMAL TRANSITION; TERT PROMOTER MUTATIONS; BREAST-CANCER; SOMATIC MUTATIONS; ANTICANCER DRUGS; TUMOR-SUPPRESSOR; HUMAN GENOME; LUNG-CANCER; EXPRESSION;

D O I：

10.1186/s13073-017-0464-7

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce mu-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying "personal" gene regulatory network. We validated mu-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. mu-cisTarget is available from http://mucistarget.aertslab.org.

引用

页数：13

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