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rascal (relative to absolute copy number scaling) 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 samples.
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 heterogeneous tumour samples may prove difficult with this method.
Please see separate wiki pages for details on how to install and use the Shiny app and the underlying R functions.
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
The rascal package is made available under the MIT license.