Journal article
MMBIRFinder: A Tool to Detect Microhomology-Mediated Break-Induced Replication
IEEE/ACM transactions on computational biology and bioinformatics, Vol.12(4), pp.799-806
07/2015
DOI: 10.1109/TCBB.2014.2359450
PMCID: PMC4857593
PMID: 26357319
Abstract
The introduction of next-generation sequencing technologies has radically changed the way we view structural genetic events. Microhomology-mediated break-induced replication (MMBIR) is just one of the many mechanisms that can cause genomic destabilization that may lead to cancer. Although the mechanism for MMBIR remains unclear, it has been shown that MMBIR is typically associated with template-switching events. Currently, to our knowledge, there is no existing bioinformatics tool to detect these template-switching events. We have developed MMBIRFinder, a method that detects template-switching events associated with MMBIR from whole-genome sequenced data. MMBIRFinder uses a half-read alignment approach to identify potential regions of interest. Clustering of these potential regions helps narrow the search space to regions with strong evidence. Subsequent local alignments identify the template-switching events with single-nucleotide accuracy. Using simulated data, MMBIRFinder identified 83 percent of the MMBIR regions within a five nucleotide tolerance. Using real data, MMBIRFinder identified 16 MMBIR regions on a normal breast tissue data sample and 51 MMBIR regions on a triple-negative breast cancer tumor sample resulting in detection of 37 novel template-switching events. Finally, we identified template-switching events residing in the promoter region of seven genes that have been implicated in breast cancer.
Details
- Title: Subtitle
- MMBIRFinder: A Tool to Detect Microhomology-Mediated Break-Induced Replication
- Creators
- Matthew W Segar - Sch. of Med., Center for Comput. Biol. & Bioinf., Indiana Univ., Indianapolis, IN, USACynthia J Sakofsky - Dept. of Biol., Univ. of Iowa, Iowa City, IA, USAAnna Malkova - Dept. of Biol., Univ. of Iowa, Iowa City, IA, USAYunlong Liu - Sch. of Med., Center for Comput. Biol. & Bioinf., Indiana Univ., Indianapolis, IN, USA
- Resource Type
- Journal article
- Publication Details
- IEEE/ACM transactions on computational biology and bioinformatics, Vol.12(4), pp.799-806
- DOI
- 10.1109/TCBB.2014.2359450
- PMID
- 26357319
- PMCID
- PMC4857593
- NLM abbreviation
- IEEE/ACM Trans Comput Biol Bioinform
- ISSN
- 1545-5963
- eISSN
- 1557-9964
- Publisher
- IEEE
- Grant note
- GM084242 / NIH (10.13039/100000002) ABI-1062432 / US National Science Foundation (10.13039/100000001)
- Language
- English
- Date published
- 07/2015
- Academic Unit
- Biology
- Record Identifier
- 9984217420302771
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