Can Mutect2 calls tumor sample specific SNV under joint calling mode?
REQUIRED for all errors and issues:
a) GATK version used: v4.2.6.1
b) Exact command used: see below
c) Entire program log: see below
Hi,
I want to ask whether Mutect2 can call tumor sample-specific mutations under multi-sample mode. For example, I have three biopsy samples taken from a patient with cancer: two from the tumors (PAAD11M and PAAD11T) and the other from a matched normal tissue (PAAD11N). And then I called mutations using Mutect2 as follows:
gatk --java-options '-Xmx5g' Mutect2 \
-R /data/reference/gatk_resource/Homo_sapiens_assembly38.fasta \
--intervals /data/reference/WES/S07604514_Regions.bed \
--interval-padding 100 -I /data/xieduo/Immun_genomics/data/Łuksza_2022_Nature/bam/PAAD11M.bam \
-I /data/xieduo/Immun_genomics/data/Łuksza_2022_Nature/bam/PAAD11T.bam \
-I /data/xieduo/Immun_genomics/data/Łuksza_2022_Nature/bam/PAAD11N.bam \
-normal PAAD11N --germline-resource /data/reference/gatk_resource/af-only-gnomad.hg38.vcf.gz
--panel-of-normals /data/xieduo/Immun_genomics/data/Łuksza_2022_Nature/results/1.PoN/pon.vcf.gz
-O /data/xieduo/Immun_genomics/data/Łuksza_2022_Nature/results/2.Mutect/PAAD11_somatic.snv.vcf
After that, I checked the PAAD11_somatic.snv.vcf file and try to find tumor sample-specific mutation (for example, the GT of a mutation in PAAD11T is 0/0 but is 0/1 in PAAD11M). However, I couldn't find any mutation that fits this pattern. Is this caused by the joint calling of multi-sample mode (the 8th point in https://gatk.broadinstitute.org/hc/en-us/articles/360050722212-FAQ-for-Mutect2)?
Thank you,
Best,
Duo
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Thank you for your post, Duo Xie ! I want to let you know we have received your question. We'll get back to you if we have any updates or follow up questions.
Please see our Support Policy for more details about how we prioritize responding to questions.
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Hi Duo Xie,
Thank you for writing to the GATK forum! I hope that we can help you sort this out.
I brought your inquiry to our developers and received some feedback to share with you.
Firstly, the GT field in Mutect2 doesn’t mean anything; it is a historical relic that we will eventually remove. You can ignore this field. Mutect2 multi-sample mode does not make sample-specific calls but rather makes a call for the individual as a whole. If there is a call that passes after filtering, it means this mutation did exist in some part of the patient’s body at some point in time. Mutect2 is not sophisticated enough to distinguish when or in which part of the body the mutation is/was.
I hope this helps to clarify things for you! Please let me know if you have any other questions in this regard. Thank you again for being a valued contributor to the GATK community.
Best,
Anthony -
Hi Duo Xie,
We haven't heard from you in a while so we're going to close out this ticket. If you still require assistance, simply respond to this email and we'll be happy to pick up where we left off!
Kind regards,
Anthony
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