TY  - JOUR
A1  - Dolzhenko, Egor
A1  - van Vugt, Joke J.F.A.
A1  - Shaw, Richard J.
A1  - Bekritsky, Mitchell A.
A1  - van Blitterswijk, Marka
A1  - Narzisi, Giuseppe
A1  - Ajay, Subramanian S.
A1  - Rajan, Vani
A1  - Lajoie, Bryan R.
A1  - Johnson, Nathan H.
A1  - Kingsbury, Zoya
A1  - Humphray, Sean J.
A1  - Schellevis, Raymond D.
A1  - Brands, William J.
A1  - Baker, Matt
A1  - Rademakers, Rosa
A1  - Kooyman, Maarten
A1  - Tazelaar, Gijs H.P.
A1  - van Es, Michael A.
A1  - McLaughlin, Russell
A1  - Sproviero, William
A1  - Shatunov, Aleksey
A1  - Jones, Ashley
A1  - Al Khleifat, Ahmad
A1  - Pittman, Alan
A1  - Morgan, Sarah
A1  - Hardiman, Orla
A1  - Al-Chalabi, Ammar
A1  - Shaw, Chris
A1  - Smith, Bradley
A1  - Neo, Edmund J.
A1  - Morrison, Karen
A1  - Shaw, Pamela J.
A1  - Reeves, Catherine
A1  - Winterkorn, Lara
A1  - Wexler, Nancy S.
A1  - The US–Venezuela Collaborative Research Group
A1  - Housman, David E.
A1  - Ng, Christopher W.
A1  - Li, Alina L.
A1  - Taft, Ryan J.
A1  - van den Berg, Leonard H.
A1  - Bentley, David R.
A1  - Veldink, Jan H.
A1  - Eberle, Michael A.
T1  - Detection of long repeat expansions from PCR-free whole-genome sequence data
Y1  - 2017/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1895 
EP  - 1903 
DO  - 10.1101/gr.225672.117 
VL  - 27 
IS  - 11 
UR  - http://genome.cshlp.org/content/27/11/1895.abstract 
N2  - Identifying large expansions of short tandem repeats (STRs), such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome, is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step toward integrating WGS into precision medicine. We developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2786/2789, 95% CI [0.997, 1.00]) of the wild-type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples in which every sample had one of eight different pathogenic repeat expansions, including those associated with fragile X syndrome, Friedreich's ataxia, and Huntington's disease, and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions. 
ER  -