Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network.

Dhingra, Priyanka; Martinez-Fundichely, Alexander; Berger, Adeline; Huang, Franklin W; Forbes, Andre Neil; Liu, Eric Minwei; Liu, Deli; Sboner, Andrea; Tamayo, Pablo; Rickman, David S; Rubin, Mark Andrew; Khurana, Ekta (2017). Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network. Genome biology, 18(1), p. 141. BioMed Central Ltd. 10.1186/s13059-017-1266-3

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We report a novel computational method, RegNetDriver, to identify tumorigenic drivers using the combined effects of coding and non-coding single nucleotide variants, structural variants, and DNA methylation changes in the DNase I hypersensitivity based regulatory network. Integration of multi-omics data from 521 prostate tumor samples indicated a stronger regulatory impact of structural variants, as they affect more transcription factor hubs in the tissue-specific network. Moreover, crosstalk between transcription factor hub expression modulated by structural variants and methylation levels likely leads to the differential expression of target genes. We report known prostate tumor regulatory drivers and nominate novel transcription factors (ERF, CREB3L1, and POU2F2), which are supported by functional validation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

UniBE Contributor:

Rubin, Mark Andrew

Subjects:

500 Science
500 Science > 570 Life sciences; biology

ISSN:

1465-6906

Publisher:

BioMed Central Ltd.

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

22 Feb 2018 16:23

Last Modified:

27 Oct 2019 10:03

Publisher DOI:

10.1186/s13059-017-1266-3

PubMed ID:

28750683

Uncontrolled Keywords:

Cancer drivers DNA methylation Prostate cancer Single nucleotide variants Structural variants Tissue-specific regulatory network

BORIS DOI:

10.7892/boris.110764

URI:

https://boris.unibe.ch/id/eprint/110764

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