Abstract
Genomic structural variants (SV) play a significant role in the onset and progression of cancer. Genomic deletions can create oncogenic fusion genes or cause the loss of tumor suppressing gene function which can lead to tumorigenesis by downregulating these genes. Detecting these variants has clinical importance in the treatment of diseases. Furthermore, it is also clinically important to detect their breakpoint boundaries at high resolution. We have generalized the framework of a previously-published algorithm that located translocations, and we have applied that framework to develop a method to locate deletions at base pair level using next-generation sequencing data. Our method uses abnormally mapped read pairs, and then subsequently maps split reads to identify precise breakpoints. On a primary prostate cancer dataset and a simulated dataset, our method predicted the number, type, and breakpoints of biologically validated SVs at high accuracy. It also outperformed two existing algorithms on precise breakpoint prediction, which is clinically important. Our algorithm, called Pegasus, accurately calls deletion breakpoints. However, the method must be extended to allow for germline variant filtering and heterozygous deletion de...Continue Reading
References
Apr 5, 2002·Genome Research·W James Kent
Jul 27, 2004·Science·Jonathan SebatMichael Wigler
May 17, 2005·Nature Genetics·Eray TuzunEvan E Eichler
Nov 24, 2006·Nature·Richard RedonMatthew E Hurles
Mar 16, 2007·Nature Reviews. Cancer·Felix MitelmanFredrik Mertens
May 15, 2007·Nature·UNKNOWN Human Genome Structural Variation Working GroupRobert H Waterston
May 5, 2009·European Urology·Scott A TomlinsJack A Schalken
May 30, 2009·Bioinformatics·Suzanne SindiBenjamin J Raphael
Aug 12, 2009·Nature Methods·Ken ChenElaine R Mardis
Jan 19, 2010·Bioinformatics·Heng Li, Richard Durbin
Feb 11, 2011·Nature·Michael F BergerLevi A Garraway
Jun 15, 2011·Nature Methods·Jianmin WangJinghui Zhang
Sep 11, 2012·Bioinformatics·Tobias RauschJan O Korbel
Jun 14, 2013·BMC Bioinformatics·Matthew Hayes, Jing Li
Feb 8, 2014·Trends in Genetics : TIG·Diego OttavianiDenise Sheer
May 23, 2015·Briefings in Bioinformatics·Christoph Bartenhagen, Martin Dugas
Jun 14, 2015·Bioinformatics·Junho KimDoheon Lee
Jan 8, 2016·Bioinformatics·Daria IakovishinaValentina Boeva
Sep 17, 2016·Bioinformatics·Ying LiangKeqin Li