Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network.
Détails
ID Serval
serval:BIB_F7C0195FB780
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network.
Périodique
Genome biology
ISSN
1474-760X (Electronic)
ISSN-L
1474-7596
Statut éditorial
Publié
Date de publication
27/07/2017
Peer-reviewed
Oui
Volume
18
Numéro
1
Pages
141
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: epublish
Publication Status: epublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
15/07/2020 11:07
Dernière modification de la notice
16/07/2020 9:43
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