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How to obtain cancer cell fraction of each mutation in subclones of a single sample

Hi All,

I am working on a project focusing on phylogeny of a specific type of tumor using single sample from multiple patients. It seems REVOLVER (manuscript link) could serve this purpose. However, its input requires cancer cell fraction (CCF) of point mutations in subclones of each sample. I know that expands the R package characterizes subpopulations in a single tumor sample. Still, further analysis can not be performed due to lack of CCF information. Is there any way to get this kind of data for REVOLVER?

tumor phylogeny revolver r

REVOLVER is written in R and is neither implemented in CRAN nor Bioconductor. It is beyond me how it made it through peer review at Nature Methods. It is failing builds over on its GitHub page. https://github.com/caravagn/revolver

As it looks like it is about to enter the dust pile, I suggest that you contact the author. You will find the email on the GitHub page.

Kevin

Hello Kevin Blighe, this is Giulio, the author of the tool, and am I here to reassure you that the tool is not entering the "dust pile".

The tool has not yet been included in neither CRAN or Bioconductor because I thought that GitHub would be enough to give support to users, but we will consider including it in a repository if this makes a major difference. The travis build failure will be fixed soon, but relates to things that do not affect the package functioning (rather an import of another package of mine whose link got broken or something).

Giulio

I can confirm that your package compiles properly via devtools.

Grazie mille, Giulio. Sarebbe buono di vedere il tuo programma nel CRAN oppure Bioconductor, così, il codice (e funzionamento) verrebbe esaminato. Nature Methods non ha stato richiesto questo?

[Thanks very much, Giulio. It would be good to see your program in CRAN or Bioconductor, thus, the code (and functioning) would be reviewed. Nature Methods did not request this?]

Hi Kevin [ciao!], during the review process a tarball of the package was provided, and everybody seemed satisfied with it (running etc). The current package contains also all the data and scripts to replicate alla the analysis of the paper. The package installs and run from the main branch, as confirmed also by the answer above, and I have been providing support through the issue page as much as possible. I did not include REVOLVER in Bioconductor yet - where I have another package, TRONCO - because I did not have time to prepare code coverage etc., but in the next few months I am planning to include it in that archive as well. There is some rewriting ongoing that I want to complete before all this happens though.

1 answer

Hi fantastycrane, the GitHub space for REVOLVER contains a wiki with some FAQ, and vignettes that you might want to look at if you decide to use the tool. Concerning your CCF-related question, to explain it shortly CCF estimates - and their clusters - are computed doing what we call "subclonal deconvolution", which requires 1) SNV 2) copy number calls, and 3) tumour purity estimation (contamination of non-tumour cells in the bulk sample). With that data there are several tools that you can use to compute the CCF values, and their clusters. Two tools that I like are pyClone and sciClone etc, for which you find support either here, or on the tool webpage.

So that bit of the analysis does not happen within REVOLVER because there are dedicated tools for it. Feel free to drop a line if you try that analysis and something does not work out for you. For questions regarding REVOLVER etc, you can also use the GitHub issue page.

REVOLVER Wiki: https://github.com/caravagn/revolver/wiki Issues: https://github.com/caravagn/revolver/issues sciClone: https://github.com/genome/sciclone pyClone: https://github.com/aroth85/pyclone

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