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gerstung-lab / MutationTimeR

An R package to time somatic mutations
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clonal_frequency clarification #5

Closed Sames-Jtudd closed 4 years ago

Sames-Jtudd commented 4 years ago

HI there , quick question when its says "clonal_frequency of each segment" in regards to the "bb" file used as input. This would suggest to me that means the proporation of tumour cells with a given copy in that segment. In Battenberg parlance the "frac1_A" or "frac1_B", this would therefore not be the same for all segments. However in the example (https://github.com/gerstung-lab/MutationTimeR/blob/master/man/MutationTimeR.Rd) the clonal freqnecy is set as 0.8 of all segments, suggesting that it is the purity of the tumour sample (aka in Battenberg parlance the cellularity). This would therefore be the same for each segment.

If you could clarify which one is the correct input Id be grateful. Many thanks Jamie

mg14 commented 4 years ago

Hi Jamie clonal_frequency is measured as cellular proportion, rather than cancer cell fraction. So for clonal segments found in all cancer cells: clonal_frequency = purity (or cellularity) Perhaps confusingly named indeed. Cheers Moritz

mg14 commented 4 years ago

Hi Jamie clonal_frequency is measured as cellular proportion, rather than cancer cell fraction. So for clonal segments found in all cancer cells: clonal_frequency = purity (or cellularity) Perhaps confusingly named indeed. Cheers Moritz

Sames-Jtudd commented 4 years ago

Thanks for the clarification

Jamie

From: Moritz Gerstung notifications@github.com Sent: 06 March 2020 11:00 To: gerstung-lab/MutationTimeR MutationTimeR@noreply.github.com Cc: James Studd James.Studd@icr.ac.uk; Author author@noreply.github.com Subject: Re: [gerstung-lab/MutationTimeR] clonal_frequency clarification (#5)

Hi Jamie clonal_frequency is measured as cellular proportion, rather than cancer cell fraction. So for clonal segments found in all cancer cells: clonal_frequency = purity (or cellularity) Perhaps confusingly named indeed. Cheers Moritz

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b-niu commented 4 years ago

Hi Jamie clonal_frequency is measured as cellular proportion, rather than cancer cell fraction. So for clonal segments found in all cancer cells: clonal_frequency = purity (or cellularity) Perhaps confusingly named indeed. Cheers Moritz

Dear @mg14, thanks for the information. May I ask that, how to set the "clonal_frequency" for "subclonal segements?

I think there's no need to consider anything about "subclonal"...

carladosanjos commented 4 years ago

Dear Moritz,

Many thanks for the previous explanation.

Still, it is not clear to me how you ended up with the clonal_frequency in the template data and how it is related to purity. Purity/cellularity is measured as cellular proportion regarding a tumor sample, not a genome segment. I understand the concept that and subclonals must have proportion < purity, but the previous given definition that clonal_frequency = purity (or cellularity), does not make much sense as it is not given for each segment. Also, regarding the template data provided, how come the clonal_frequency can be the same for segments with different major_cn and minor_cn.

I am trying to figure out where the clonal_frequency of segments come from. My question is how did you generated the clonal_frequency for each segment (as a data.frame), specially the subclonals? Is it the output of any software, such as ABSOLUTE, or did you estimated it based on cell prevalence or other variable for each segment?

Many thanks!

mg14 commented 4 years ago

For a clonal copy number segment,clonal_frequency = purity. In the example provided all segments are clonal.

If there was a subclonal copy number segment (eg. from ABSOLUTE or Battenberg) one has two entries in the GRanges object with identical coordinates, but different major_cn and/or minor_cn as well as clonal_frequency values. The sum of the two clonal_frequency values for that region needs to equal purity.

Please note that a priori it is not clear which of the two configurations is ancestral and which one the derived (ie more recent) state. Usually it would be natural to assume that the diploid state is ancestral, but it doesn't have to be as in the case of WGD. For point mutations one usually does not specify the ancestral state, as it is implicitly assumed to be that of the matched normal.

shaghayeghsoudi commented 3 years ago

Is there any example of how the CNV file should look like when there are sub clonal CNV segments?