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Matt Eldridge edited this page Jun 8, 2021 · 7 revisions

rascal

rascal is an R package and Shiny web application for scaling relative copy number data generated from shallow whole genome sequencing of cancer samples to absolute values and, in doing so, estimating the tumour ploidy and cellularity of the sample.

Description

Several research groups at the Cancer Research UK Cambridge Institute are using shallow whole genome sequencing as a relatively inexpensive method for obtaining copy number profiles for tumour samples, particularly as several libraries can be multiplexed in a single lane of sequencing. We are principally using the QDNAseq R package from the Bioconductor project for summing reads that align within genomic windows or bins, typically 30kb in size, and correcting for GC-content and mappability. This results in values that are relative to the average copy number within the sample for the GC and mappability of each bin. These relative copy numbers are smoothed and segmented and provide useful insight into genomic abnormalities in cancers.

For some research projects, it is desirable to obtain absolute copy numbers and normally this would require deeper whole genome sequencing from which allele fractions of germline SNPs can help determine the clonal architecture of a tumour sample. In the absence of such information, and noting the significant increase in cost for deeper sequencing, we can attempt to fit the relative copy number profiles to absolute copy numbers by evaluating various ploidy and cellularity estimates.

The approach used in this package is based on concepts introduced in the ACE package developed by Bauke Ylstra's group at Amsterdam UMC, who are also the authors of QDNAseq. The mathematics underpinning this approach assume a single dominant clone so estimating ploidy and cellularity for heterogenous tumour samples may prove difficult with this method.

## Installation and Usage

Please see separate wiki pages for details on how to install and use the Shiny app and the underlying R functions.

Acknowledgements

rascal is developed and maintained by Matt Eldridge in the CRUK CI Bioinformatics Core in collaboration with:

  • Carolin Sauer
  • Geoff Macintyre
  • James Brenton's group at CRUK CI
  • Florian Markowetz's group at CRUK CI

License

The rascal package is made available under the MIT license.

` MIT License

Copyright (c) 2021 CRUK Cambridge Institute - Bioinformatics Core

Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. `

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