RT Journal
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
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, Karren
A1 Shaw, Pam
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
JF Genome Research 
JO Genome Research 
YR 2017 
FD September 08 
DO 10.1101/gr.225672.117 
SP gr.225672.117 
UL http://genome.cshlp.org/content/early/2017/09/08/gr.225672.117.abstract 
AB 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 towards integrating WGS into precision medicine. We have 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 3,001 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% (2,786/2,789, 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 where 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. The software is licensed under GPL v3.0 and the source code is freely available on GitHub.