title: ShatterProof: operational detection and quantification of chromothripsis.
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.
authors.forename: Shaylan K
authors.initials: SK
authors.lastname: Govind
authors.forename: Amin
authors.initials: A
authors.lastname: Zia
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Hennings-Yeomans
authors.forename: John D
authors.initials: JD
authors.lastname: Watson
authors.forename: Michael
authors.initials: M
authors.lastname: Fraser
authors.forename: Catalina
authors.initials: C
authors.lastname: Anghel
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Wyatt
authors.forename: Theodorus
authors.initials: T
authors.lastname: van der Kwast
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.forename: John D
authors.initials: JD
authors.lastname: McPherson
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.affiliation: Ontario Institute for Cancer Research, M5G 0A3, Toronto, Canada. Paul.Boutros@oicr.on.ca.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
mesh_terms: D000465:Algorithms; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics; D017422:Sequence Analysis, DNA; D012984:Software