TY - JOUR
T1 - ShatterProof
T2 - Operational detection and quantification of chromothripsis
AU - Govind, Shaylan K.
AU - Zia, Amin
AU - Hennings-Yeomans, Pablo H.
AU - Watson, John D.
AU - Fraser, Michael
AU - Anghel, Catalina
AU - Wyatt, Alexander W.
AU - van der Kwast, Theodorus
AU - Collins, Colin C.
AU - Mcpherson, John Douglas
AU - Bristow, Robert G.
AU - Boutros, Paul C.
PY - 2014/3/19
Y1 - 2014/3/19
N2 - Background: Chromothripsis, a newly discovered type of complex genomic rearrangement, has been implicated in the evolution of several types of cancers. To date, it has been described in bone cancer, SHH-medulloblastoma and acute myeloid leukemia, amongst others, however there are still no formal or automated methods for detecting or annotating it in high throughput sequencing data. As such, findings of chromothripsis are difficult to compare and many cases likely escape detection altogether.Results: We introduce ShatterProof, a software tool for detecting and quantifying chromothriptic events. ShatterProof takes structural variation calls (translocations, copy-number variations, short insertions and loss of heterozygosity) produced by any algorithm and using an operational definition of chromothripsis performs robust statistical tests to accurately predict the presence and location of chromothriptic events. Validation of our tool was conducted using clinical data sets including matched normal, prostate cancer samples in addition to the colorectal cancer and SCLC data sets used in the original description of chromothripsis.Conclusions: ShatterProof is computationally efficient, having low memory requirements and near linear computation time. This allows it to become a standard component of sequencing analysis pipelines, enabling researchers to routinely and accurately assess samples for chromothripsis. Source code and documentation can be found at http://search.cpan.org/~sgovind/Shatterproof.
AB - Background: Chromothripsis, a newly discovered type of complex genomic rearrangement, has been implicated in the evolution of several types of cancers. To date, it has been described in bone cancer, SHH-medulloblastoma and acute myeloid leukemia, amongst others, however there are still no formal or automated methods for detecting or annotating it in high throughput sequencing data. As such, findings of chromothripsis are difficult to compare and many cases likely escape detection altogether.Results: We introduce ShatterProof, a software tool for detecting and quantifying chromothriptic events. ShatterProof takes structural variation calls (translocations, copy-number variations, short insertions and loss of heterozygosity) produced by any algorithm and using an operational definition of chromothripsis performs robust statistical tests to accurately predict the presence and location of chromothriptic events. Validation of our tool was conducted using clinical data sets including matched normal, prostate cancer samples in addition to the colorectal cancer and SCLC data sets used in the original description of chromothripsis.Conclusions: ShatterProof is computationally efficient, having low memory requirements and near linear computation time. This allows it to become a standard component of sequencing analysis pipelines, enabling researchers to routinely and accurately assess samples for chromothripsis. Source code and documentation can be found at http://search.cpan.org/~sgovind/Shatterproof.
KW - Bioinformatics
KW - Chromothripsis
KW - Complex genomic rearrangement
KW - High throughput sequencing
KW - Next generation sequencing
KW - Perl
UR - http://www.scopus.com/inward/record.url?scp=84899054169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899054169&partnerID=8YFLogxK
U2 - 10.1186/1471-2105-15-78
DO - 10.1186/1471-2105-15-78
M3 - Article
C2 - 24646301
AN - SCOPUS:84899054169
VL - 15
JO - BMC Bioinformatics
JF - BMC Bioinformatics
SN - 1471-2105
IS - 1
M1 - 78
ER -