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Apparent difference between active region algorithm in mutect.pdf and Mutect2Engine.java:492

SullySully Galway, Ireland.Member
Hello,

First off, thank you so much for an excellent toolkit and brilliant forum.
Both have and continue to help me out so much in my work. I am very grateful.

My question relates to an apparent difference in MuTect, GATK4, between the algorithm for identifying active regions (as outlined in docs/mutect/mutect.pdf, page 2) and how it is implemented in the MuTect source file tools/walkers/mutect/Mutect2Engine.java, line 492.

In the code (Mutect2Engine.java:492), fTildeRatio is evaluated as,

```
fTildeRatio = FastMath.exp(MathUtils.digamma(nRef + 1) - MathUtils.digamma(nAlt + 1));
```

However, in mutect.pdf, page 2, just after equation 1, it appears to indicate it should be evaluated as,

```
fTildeRatio = FastMath.exp(MathUtils.digamma(nRef + 1) - MathUtils.digamma(n + 2));
```

Is there a dependency there and if so how and in what situations would it affect the ultimate TLOD value in the vcf file?

Apologies in advance if I'm missing something here or it has been answered before.
I haven't come across it as yet.

Thanks again and best regards, Brian
Tagged:

Answers

  • bhanuGandhambhanuGandham Cambridge MAMember, Administrator, Broadie, Moderator admin

    Hi ,

    The GATK support team is focused on resolving questions about GATK tool-specific errors and abnormal/erroneous results from the tools. For all other questions, such as this one, we are building a backlog to work through when we have the capacity.

    Please continue to post your questions because we will be mining them for improvements to documentation, resources, and tools.

    We cannot guarantee a reply, however, we ask other community members to help out if you know the answer.

    For context, see this [announcement](https://software.broadinstitute.org/gatk/blog?id=24419 “announcement”) and check out our [support policy](https://gatkforums.broadinstitute.org/gatk/discussion/24417/what-types-of-questions-will-the-gatk-frontline-team-answer/p1?new=1 “support policy”).

  • davidbendavidben BostonMember, Broadie, Dev ✭✭✭

    @Sully Thank you for a sharp-eyed question! The docs and code are both correct, because we define

    fTildeRef = FastMath.exp(MathUtils.digamma(nRef + 1) - MathUtils.digamma(n + 2));
    fTildeAlt = FastMath.exp(MathUtils.digamma(nAlt + 1) - MathUtils.digamma(n + 2));
    

    and hence their ratio fTileRef/fTildeAlt is

    fTildeRatio = FastMath.exp(MathUtils.digamma(nRef + 1) - MathUtils.digamma(n + 2) - MathUtils.digamma(nAlt + 1) + MathUtils.digamma(n + 2));
       = FastMath.exp(MathUtils.digamma(nRef + 1)- MathUtils.digamma(nAlt + 1));
    

    as desired.

    Regards,
    David

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