DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer

被引：222

作者：

Bashashati, Ali ^{[1
]}

Haffari, Gholamreza ^{[1
,2
]}

Ding, Jiarui ^{[1
,3
]}

Ha, Gavin ^{[1
,4
]}

Lui, Kenneth ^{[1
]}

Rosner, Jamie ^{[1
]}

Huntsman, David G. ^{[5
,6
]}

Caldas, Carlos ^{[7
]}

Aparicio, Samuel A. ^{[1
,5
]}

Shah, Sohrab P. ^{[1
,3
,5
]}

机构：

[1] British Columbia Canc Agcy, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada

[2] Monash Univ, Fac Informat Technol, Clayton, Vic 3800, Australia

[3] Univ British Columbia, Dept Comp Sci, Vancouver, BC V6T 1Z4, Canada

[4] Univ British Columbia, Bioinformat Training Program, Vancouver, BC V5Z 4S6, Canada

[5] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada

[6] BC Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada

[7] Li Ka Shing Ctr, Canc Res UK, Cambridge Res Inst, Cambridge CB2 0RE, England

来源：

GENOME BIOLOGY | 2012年 / 13卷 / 12期

关键词：

driver mutations; sequencing; cancer; transcriptional networks; PATHWAYS; GENES; COLON;

D O I：

10.1186/gb-2012-13-12-r124

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Simultaneous interrogation of tumor genomes and transcriptomes is underway in unprecedented global efforts. Yet, despite the essential need to separate driver mutations modulating gene expression networks from transcriptionally inert passenger mutations, robust computational methods to ascertain the impact of individual mutations on transcriptional networks are underdeveloped. We introduce a novel computational framework, DriverNet, to identify likely driver mutations by virtue of their effect on mRNA expression networks. Application to four cancer datasets reveals the prevalence of rare candidate driver mutations associated with disrupted transcriptional networks and a simultaneous modulation of oncogenic and metabolic networks, induced by copy number co-modification of adjacent oncogenic and metabolic drivers. DriverNet is available on Bioconductor or at http://compbio.bccrc.ca/software/drivernet/.

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