Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network.
Details
Serval ID
serval:BIB_F7C0195FB780
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network.
Journal
Genome biology
ISSN
1474-760X (Electronic)
ISSN-L
1474-7596
Publication state
Published
Issued date
27/07/2017
Peer-reviewed
Oui
Volume
18
Number
1
Pages
141
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
Algorithms, Binding Sites, Carcinogenesis/genetics, Carcinogenesis/metabolism, Carcinogenesis/pathology, Chromosome Mapping, Cyclic AMP Response Element-Binding Protein/genetics, Cyclic AMP Response Element-Binding Protein/metabolism, DNA Methylation, Deoxyribonuclease I, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Male, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Octamer Transcription Factor-2/genetics, Octamer Transcription Factor-2/metabolism, Organ Specificity, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Protein Binding, Protein Interaction Mapping, Repressor Proteins/genetics, Repressor Proteins/metabolism, Cancer drivers, DNA methylation, Prostate cancer, Single nucleotide variants, Structural variants, Tissue-specific regulatory network
Pubmed
Web of science
Open Access
Yes
Create date
15/07/2020 11:07
Last modification date
16/07/2020 9:43
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