Open AccessGenome-wide detection of enhancer-hijacking events from chromatin interaction data in rearranged genomes
Author(s) -
Xiaotao Wang,
Jie Xu,
Baozhen Zhang,
Ye Hou,
Fan Song,
Huijue Lyu,
Feng Yue
Publication year - 2021
Publication title -
nature methods
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 19.469
H-Index - 318
eISSN - 1548-7105
pISSN - 1548-7091
DOI - 10.1038/s41592-021-01164-w
Subject(s) - chromatin , enhancer , biology , computational biology , crispr , genome , chia pet , genetics , breakpoint , cas9 , gene , chromatin remodeling , chromosomal translocation , transcription factor
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.