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Genome-wide detection of enhancer-hijacking events from chromatin interaction data in rearranged genomes
- Source :
- Nat Methods
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Recent efforts have shown that structural variations (SVs) can disrupt three-dimensional genome organization and induce enhancer hijacking, yet no computational tools exist to identify such events from chromatin interaction data. Here, we develop NeoLoopFinder, a computational framework to identify the chromatin interactions induced by SVs, including interchromosomal translocations, large deletions and inversions. Our framework can automatically resolve complex SVs, reconstruct local Hi-C maps surrounding the breakpoints, normalize copy number variation and allele effects and predict chromatin loops induced by SVs. We applied NeoLoopFinder in Hi-C data from 50 cancer cell lines and primary tumors and identified tens of recurrent genes associated with enhancer hijacking. To experimentally validate NeoLoopFinder, we deleted the hijacked enhancers in prostate adenocarcinoma cells using CRISPR–Cas9, which significantly reduced expression of the target oncogene. In summary, NeoLoopFinder enables identification of critical oncogenic regulatory elements that can potentially reveal therapeutic targets. This work presents NeoLoopFinder, a computational method, for identifying chromatin interactions of structurally rearranged genomes. NeoLoopFinder was applied in 50 cancer datasets and identified genes associated with enhancer-hijacking events.
- Subjects :
- Developmental Disabilities
Computational biology
Biology
Real-Time Polymerase Chain Reaction
Biochemistry
Genome
Article
03 medical and health sciences
Humans
Copy-number variation
Allele
Enhancer
Molecular Biology
Gene
030304 developmental biology
Genomic organization
0303 health sciences
Genome, Human
Breakpoint
Cell Biology
Chromatin
Enhancer Elements, Genetic
Genomic Structural Variation
CRISPR-Cas Systems
K562 Cells
Algorithms
Protein Binding
Biotechnology
Subjects
Details
- ISSN :
- 15487105 and 15487091
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Nature Methods
- Accession number :
- edsair.doi.dedup.....c3ef651b4eef2bb8b1b1ed32c18e8ef7