Atomize Mutect2 MNV variants?

[sorelfitzgibbon]

MNVs are in-phase neighboring SNVs. On somewhat rare occasions they can code for a codon change which is not reflected in any of the individual SNVs, e.g. a stop codon.

But this is an SNV pipeline so the SNVs have been separated from MNVs and indels. I'm not sure whether to break the MNVs into their component SNVs and merge them back in with the other SNVs. This seems like the right thing to do, along with keeping the MNVs VCF in the output, but it could be confusing.

Variant Counts

..._pass_indels.vcf.gz 838
..._pass_mnps.vcf.gz 88
..._pass_snps.vcf.gz 1691
..._pass.vcf.gz 2617

[pboutros]

Definitely no to splitting MNVs. It’s fundamentally different from a cancer perspective to have: AA --> AB --> BB (two mutational events) Vs. AA --> BB (one mutational event) We have to trust that the caller is getting this correct and is suggesting that an MNV is one event not two (or at least that there’s no evidence to support two) From: Sorel Fitz-Gibbon ***@***.***> Sent: Wednesday, April 12, 2023 6:52 PM To: uclahs-cds/pipeline-call-sSNV ***@***.***> Cc: Subscribed ***@***.***> Subject: [uclahs-cds/pipeline-call-sSNV] Atomize `Mutect2` MNV variants? (Discussion #172) CAUTION - EXTERNAL EMAIL:Do not click links or open attachments unless you recognize the sender. MNVs are in-phase neighboring SNVs. On somewhat rare occasions they can code for a codon change which is not reflected in any of the individual SNVs, e.g. a stop codon. But this is an SNV pipeline so the SNVs have been separated from MNVs and indels. I'm not sure whether to break the MNVs into their component SNVs and merge them back in with the other SNVs. This seems like the right thing to do, along with keeping the MNVs VCF in the output, but it could be confusing. Variant Counts ..._pass_indels.vcf.gz 838 ..._pass_mnps.vcf.gz 88 ..._pass_snps.vcf.gz 1691 ..._pass.vcf.gz 2617 — Reply to this email directly, view it on GitHub<https://urldefense.com/v3/__https:/github.com/uclahs-cds/pipeline-call-sSNV/discussions/172__;!!F9wkZZsI-LA!D9NDKCDOxFV07WfZsdpN_80ao_q8cF7kk6M-FSX2UNTMWUGoYUZ8QZXb3Y7ZJCBkVoaoAv2wOpjUJ1Oe_NkV7VbCCxzUa84$>, or unsubscribe<https://urldefense.com/v3/__https:/github.com/notifications/unsubscribe-auth/AB3YOXT3XJZ3C3XUTOU43TDXA5L33ANCNFSM6AAAAAAW4NQE74__;!!F9wkZZsI-LA!D9NDKCDOxFV07WfZsdpN_80ao_q8cF7kk6M-FSX2UNTMWUGoYUZ8QZXb3Y7ZJCBkVoaoAv2wOpjUJ1Oe_NkV7VbClkgHmt8$>. You are receiving this because you are subscribed to this thread.Message ID: ***@***.******@***.***>>

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[sorelfitzgibbon]

OK, but if I understand correctly we won't be using these MNVs downstream (in this pipeline). Would they have been called as SNVs if Mutect2 was not looking for MNVs? You would rather they are not counted at all?

[pboutros]

I’m not sure of the question here? From: Sorel Fitz-Gibbon ***@***.***> Sent: Wednesday, April 12, 2023 7:04 PM To: uclahs-cds/pipeline-call-sSNV ***@***.***> Cc: Boutros, Paul C. ***@***.***>; Comment ***@***.***> Subject: Re: [uclahs-cds/pipeline-call-sSNV] Atomize `Mutect2` MNV variants? (Discussion #172) CAUTION - EXTERNAL EMAIL:Do not click links or open attachments unless you recognize the sender. OK, but if I understand correctly we won't be using these MNVs downstream (in this pipeline). Would they have been called as SNVs if Mutect2 was not looking for MNVs? You would rather they are not counted at all? — Reply to this email directly, view it on GitHub<https://urldefense.com/v3/__https:/github.com/uclahs-cds/pipeline-call-sSNV/discussions/172*discussioncomment-5598999__;Iw!!F9wkZZsI-LA!GtvuJX42sGQvsP8U-6iYRwXYSnnb_K_h9-dds4LkWr8trSBM6Cz6GPH3b54MmKdnVZGwik6h-IQ_bwZkjZNoo-LhDm0C3MA$>, or unsubscribe<https://urldefense.com/v3/__https:/github.com/notifications/unsubscribe-auth/AB3YOXVQR5TG5MM7ZNP4DJDXA5NKVANCNFSM6AAAAAAW4NQE74__;!!F9wkZZsI-LA!GtvuJX42sGQvsP8U-6iYRwXYSnnb_K_h9-dds4LkWr8trSBM6Cz6GPH3b54MmKdnVZGwik6h-IQ_bwZkjZNoo-LhsdHcODg$>. You are receiving this because you commented.Message ID: ***@***.******@***.***>>

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[sorelfitzgibbon]

Are you saying to keep the MNVs in the mutect2.snvs.vcf.gz that will be intersected with the SNVs from the other tools? If so,

• what about the indels, keep or not? All of the other tools output an SNV-only file (Strelka outputs an additional indel file)
• the intersection will have to be done carefully to make sure overlaps are considered.

[pboutros]

Oh, I didn’t make any comment on that. I’m simply saying that it’s not necessarily biologically correct to treat an MNV as its constitutive SNVs From: Sorel Fitz-Gibbon ***@***.***> Sent: Wednesday, April 12, 2023 7:20 PM To: uclahs-cds/pipeline-call-sSNV ***@***.***> Cc: Boutros, Paul C. ***@***.***>; Comment ***@***.***> Subject: Re: [uclahs-cds/pipeline-call-sSNV] Atomize `Mutect2` MNV variants? (Discussion #172) CAUTION - EXTERNAL EMAIL:Do not click links or open attachments unless you recognize the sender. Are you saying to keep the MNVs in the mutect2.snvs.vcf.gz that will be intersected with the SNVs from the other tools? If so, * what about the indels, keep or not? All of the other tools output an SNV-only file (Strelka outputs an additional indel file) * the intersection will have to be done carefully to make sure overlaps are considered. — Reply to this email directly, view it on GitHub<https://urldefense.com/v3/__https:/github.com/uclahs-cds/pipeline-call-sSNV/discussions/172*discussioncomment-5599096__;Iw!!F9wkZZsI-LA!Es11zpU73j42G5x-zvh1IG1wwIfh05Mzjhmz5-tafEG7fWpvsqaqBbyGL917q4ApP4B_ooVFvqMhZM617rHlWDuu0IoMcE8$>, or unsubscribe<https://urldefense.com/v3/__https:/github.com/notifications/unsubscribe-auth/AB3YOXXDOM6QEOW2VMYE23DXA5PGDANCNFSM6AAAAAAW4NQE74__;!!F9wkZZsI-LA!Es11zpU73j42G5x-zvh1IG1wwIfh05Mzjhmz5-tafEG7fWpvsqaqBbyGL917q4ApP4B_ooVFvqMhZM617rHlWDuuUGTmXbU$>. You are receiving this because you commented.Message ID: ***@***.******@***.***>>

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