Applying Mutect2 to targeted gene sequencing panels
Hello,
I would like to ask about a potential analysis using mutect2 which I am not too sure about please
If you are investigating somatic mutations in a tumour sample using targeted gene sequencing methods (e.g. looking at 30 cancer-related genes using PCR-based targeted sequencing) rather than whole exon sequencing or whole genome sequencing, is it still required to have a matched normal sample if only a very small proportion of normal samples (e.g. <1%) is expected to possess a germline mutation for each gene of interest in our panel?
A possible argument that could be made is that because the expected rate of (deleterious) germline mutations is so low, the matched normal would remove in total very few germline mutations mislabelled as somatic - and therefore there would be no/little need for a matched normal during somatic variant calling using tools such as mutect2.
I would be happy to hear any thoughts regarding this. Thank you in advance.
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Hi Thomas Bradley,
I am going to move your post into our Community Discussions -> General Discussion topic, as the Somatic topic is for reporting bugs and issues with GATK.
You can read more about our forum guidelines and the topics here: Forum Guidelines.
Best,
Genevieve
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Hello, have you seen this discussion on the forum? https://gatk.broadinstitute.org/hc/en-us/community/posts/360057810051-Mutect2-somatic-variant-calling-with-without-matched-normal-sample
As well as our Mutect2 FAQ doc? https://gatk.broadinstitute.org/hc/en-us/articles/360050722212-FAQ-for-Mutect2
There might be some information in there that can help with your use case. As far as I know, we always recommend including a matched normal if possible.
It would be great to hear from other users who are doing similar analysis, and what they chose in this case.
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Hello,
Apologies for the late reply. Thank you for the links, they were definitely informative for the question that I asked. I guess the normal samples can be useful to help detect detect technical artifacts too which may not necessarily appear in the panel of normals.
Thanks!
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