ShatterProof: Operational detection and quantification of chromothripsis

Shaylan K. Govind, Amin Zia, Pablo H. Hennings-Yeomans, John D. Watson, Michael Fraser, Catalina Anghel, Alexander W. Wyatt, Theodorus van der Kwast, Colin C. Collins, John Douglas Mcpherson, Robert G. Bristow, Paul C. Boutros

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number78
JournalBMC Bioinformatics
Volume15
Issue number1
DOIs
StatePublished - Mar 19 2014
Externally publishedYes

Keywords

  • Bioinformatics
  • Chromothripsis
  • Complex genomic rearrangement
  • High throughput sequencing
  • Next generation sequencing
  • Perl

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics
  • Structural Biology

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    Govind, S. K., Zia, A., Hennings-Yeomans, P. H., Watson, J. D., Fraser, M., Anghel, C., Wyatt, A. W., van der Kwast, T., Collins, C. C., Mcpherson, J. D., Bristow, R. G., & Boutros, P. C. (2014). ShatterProof: Operational detection and quantification of chromothripsis. BMC Bioinformatics, 15(1), [78]. https://doi.org/10.1186/1471-2105-15-78