| Title | Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Dhingra P, Martinez-Fundichely A, Berger A, Huang FW, Forbes ANeil, Liu EMinwei, Liu D, Sboner A, Tamayo P, Rickman DS, Rubin MA, Khurana E |
| Journal | Genome Biol |
| Volume | 18 |
| Issue | 1 |
| Pagination | 141 |
| Date Published | 2017 07 27 |
| ISSN | 1474-760X |
| Keywords | Algorithms, Binding Sites, Carcinogenesis, Chromosome Mapping, Cyclic AMP Response Element-Binding Protein, Deoxyribonuclease I, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Male, Nerve Tissue Proteins, Octamer Transcription Factor-2, Organ Specificity, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Prostatic Neoplasms, Protein Binding, Protein Interaction Mapping, Repressor Proteins |
| 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. |
| DOI | 10.1186/s13059-017-1266-3 |
| Alternate Journal | Genome Biol. |
| PubMed ID | 28750683 |
| PubMed Central ID | PMC5530464 |
| Grant List | R01 CA179100 / CA / NCI NIH HHS / United States R01 GM074024 / GM / NIGMS NIH HHS / United States R21 CA143496 / CA / NCI NIH HHS / United States U24 CA194107 / CA / NCI NIH HHS / United States U24 CA210989 / CA / NCI NIH HHS / United States |