title: DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer.
abstract: 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/.
authors: Ali
authors: A
authors: Bashashati
authors: Gholamreza
authors: G
authors: Haffari
authors: Jiarui
authors: J
authors: Ding
authors: Gavin
authors: G
authors: Ha
authors: Kenneth
authors: K
authors: Lui
authors: Jamie
authors: J
authors: Rosner
authors: David G
authors: DG
authors: Huntsman
authors: Carlos
authors: C
authors: Caldas
authors: Samuel A
authors: SA
authors: Aparicio
authors: Sohrab P
authors: SP
authors: Shah
mesh_terms: D000465:Algorithms; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D023281:Genomics; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes; D012984:Software; D014158:Transcription, Genetic
references: Cell. 2010 Dec 10;143(6):1005-17
references: 21129771
references: Breast Dis. 2003;18:75-86
references: 15687690
references: Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12372-7
references: 21746896
references: Bioinformatics. 2010 Jun 15;26(12):i237-45
references: 20529912
references: Nature. 2011 Jun 29;474(7353):609-15
references: 21720365
references: Mol Endocrinol. 2007 Sep;21(9):2218-32
references: 17550976
references: Genome Res. 2012 Feb;22(2):375-85
references: 21653252
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D945-50
references: 20952405
references: Bioinformatics. 2011 Jan 15;27(2):175-81
references: 21169372
references: Mol Syst Biol. 2008;4:216
references: 18766176
references: Nature. 2008 Oct 23;455(7216):1061-8
references: 18772890
references: Nature. 2012 Apr 18;486(7403):346-52
references: 22522925
references: Cancer Res. 2011 Jul 1;71(13):4550-61
references: 21555372
references: Nat Rev Cancer. 2004 Mar;4(3):177-83
references: 14993899
references: Cell. 2011 Sep 2;146(5):697-708
references: 21884932
references: EMBO Mol Med. 2011 Mar;3(3):167-80
references: 21337521
references: Science. 2008 Sep 26;321(5897):1807-12
references: 18772396
references: Nature. 2012 Jan 26;483(7387):100-3
references: 22281684
references: Nature. 2012 Oct 4;490(7418):61-70
references: 23000897
references: PLoS One. 2010 Nov 15;5(11):e13984
references: 21085593
references: Genetics. 2006 Aug;173(4):2187-98
references: 16783027
references: Nat Rev Cancer. 2011 Feb;11(2):85-95
references: 21258394
references: Nature. 2012 Jul 18;487(7407):330-7
references: 22810696
references: Nature. 2012 Apr 04;486(7403):395-9
references: 22495314
references: Genome Biol. 2010;11(5):R53
references: 20482850
references: PLoS Med. 2008 Dec 2;5(12):e232
references: 19053170
references: J Comput Biol. 2011 Mar;18(3):507-22
references: 21385051
references: Genome Res. 2012 Feb;22(2):398-406
references: 21908773
references: Science. 2007 Sep 14;317(5844):1500
references: 17872428
references: Nature. 2012 Sep 27;489(7417):519-25
references: 22960745