broadinstitute / ichorCNA

Estimating tumor fraction in cell-free DNA from ultra-low-pass whole genome sequencing.
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segments with deletions become 'red' colored #85

Open hw538 opened 3 years ago

hw538 commented 3 years ago

Hi ichorCNA team,

not sure why the delections become 'red' in our genome wide plots.

if I understand correctly, all the deletions should be 'green' colored. would you have any hints?

here is an example attached. SLX-18760_SXTHSH03.FS_1.sort_genomeWide.pdf

hw538 commented 3 years ago

in the attached pdf above, the chr 6, 9, 10, 13 have those 'red' deletions, quite strange...

gavinha commented 3 years ago

Hi @hw538

Label switching has occurred. Very likely this is a suboptimal solution and should not be selected as the final result.

I would recommend that you turn on the subclonal setting (--estimateSubclones TRUE and --scStates "c(1,3)") and or run for multiple restarts (solutions) for --normal and --ploidy.

Hope this helps.

Best, Gavin

hw538 commented 3 years ago

Thank you gavinha, for --estimateSubclones TRUE, I didn't find this option in the wiki page, would you mean --estimateScPrevalence TRUE instead?

Best, Haichao

hw538 commented 3 years ago

Thanks, by adding --estimateScPrevalence TRUE and --scStates "c(1,3)", the color label now becomes normal. and it is true that the light green seg indicating subclonal CNVs. see attached:

rerun_SLX-18760_SXTHSH03.FS_1.sort_plots_genomeWide.pdf

could I know further why a suboptimal solution would alter the color label?

(would the explanation be:

if I don't turn on the --evaluateScPrevalence option, the ichorCNA algorithm won't consider subclones, and finally, the algorithm thought it had chosen an 'optimal' path, but this one CANNOT reflect the true CNV scenario in the genome. i.e. the 'optimal' path treats those regions as 'amplification' (red-colored), but in reality, these regions are 'deletions' (green-colored).

Best, Haichao