Skip to content
New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

Zygosity annotation of mutations should be done with hisens rather than purity #967

Open
anoronh4 opened this issue Aug 23, 2022 · 1 comment · Fixed by #987
Open

Zygosity annotation of mutations should be done with hisens rather than purity #967

anoronh4 opened this issue Aug 23, 2022 · 1 comment · Fixed by #987
Assignees
Labels
bug Something isn't working
Milestone

Comments

@anoronh4
Copy link
Collaborator

anoronh4 commented Aug 23, 2022

We are currently using the purity facets result to annotate the maf, but I believe we should be using the hisens result instead. looks like the clinical impact runs are run using hisens, and for annotating point mutations i think it makes sense to use a result with less smoothing.

somatic annotation:

tempo/pipeline.nf

Lines 1838 to 1844 in 41a0bf5

Rscript --no-init-file /usr/bin/facets-suite/annotate-maf-wrapper.R \
--facets-output ${purity_rdata} \
--maf-file ${maf} \
--facets-algorithm em \
--output ${outputPrefix}.facets.maf
Rscript --no-init-file /usr/bin/annotate-with-zygosity-somatic.R ${outputPrefix}.facets.maf ${outputPrefix}.facets.zygosity.maf

germline annotation:

tempo/pipeline.nf

Lines 2335 to 2340 in 41a0bf5

Rscript --no-init-file /usr/bin/facets-suite/annotate-maf-wrapper.R \
--facets-output ${purity_rdata} \
--maf-file ${maf} \
--output ${outputPrefix}.facets.maf
Rscript --no-init-file /usr/bin/annotate-with-zygosity-germline.R ${outputPrefix}.facets.maf ${outputPrefix}.final.maf

Here is an example annotation for a variant (select columns):

Hugo_Symbol	t_var_freq	n_var_freq	tcn	lcn	cf	purity	expected_alt_copies	allelic_imbalance	loss_of_heterozygosity	zygosity_flag
BRCA2	0.69811320754717	0.541666666666667	2	1	1	0.521339308396323	3	ALT_GAIN	TRUE	AI_LOH_ALT

We found that this led to tcn and lcn annotations in the maf that we didn't expect, for example in the following variant, tcn/lcn was 2/1, but the zygosity flag said that there was LOH. Taken together, purity and t_var_freq would suggest that it is in fact LOH. The hisens copy number says that the segment would be 1/0, and would be harmonious with t_var_freq (if i understand it correctly).

@anoronh4 anoronh4 added this to the 2.0 milestone Aug 31, 2022
@anoronh4
Copy link
Collaborator Author

Should be noted in release notes for v2.

@anoronh4 anoronh4 self-assigned this Sep 2, 2022
@gongyixiao gongyixiao added the bug Something isn't working label Mar 16, 2023
@anoronh4 anoronh4 linked a pull request Jun 30, 2023 that will close this issue
Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment
Labels
bug Something isn't working
Projects
None yet
Development

Successfully merging a pull request may close this issue.

2 participants