Mutect2 gets different results when I change the downsample level

I use mutect2 of GATK 3.6 and GATK 3.7 to call variant. I know there is a downsampling in mutect2 which has an important influence on the result. So I change the downsampling level. For example: the default value is:

 maxReadsInRegionPerSample = 1000;
 minReadsPerAlignmentStart = 5;

I change these parameters to a bigger one:

 maxReadsInRegionPerSample = 2000;
 minReadsPerAlignmentStart = 10;

Then I compile the code, run it and get the result named downsample_2x.vcf. However, compared to the default result original.vcf, the result is very strange:

There are more variants in downsample_2x.vcf, which is easy to understand because there are much more samples. However, there are also less variants in downsample_2x.vcf(That is, variants in original.vcf are not show in downsample_2x.vcf, around 200 within total 900 variants). Since the sample get bigger, why there are less variants? It's difficult for me to understand. If the result with more samples is much more accurate, how about these missing 200 variants?Any reply will be much appreicated!

Tagged:

Answers

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin
    The downsampling system used in the GATK 3 version of MuTect2 is excessively complicated, and has some side effects like this that are difficult to handle. I would encourage you to either not touch the default downsampling settings or (better) switch to using the version that is included in GATK4. This will be released as a beta version very soon.
  • @Geraldine_VdAuwera said:
    The downsampling system used in the GATK 3 version of MuTect2 is excessively complicated, and has some side effects like this that are difficult to handle. I would encourage you to either not touch the default downsampling settings or (better) switch to using the version that is included in GATK4. This will be released as a beta version very soon.

    Thanks Geraldine. But I find that maxReadsInRegionPerSample and minReadsPerAlignmentStart are two parameters in the mutect2 documentation of GATK 3.7. And I also found there is a question about how to change the downsampling level. So, if the mutect2 provide these two parameters, how should I use it correctly? Thanks in advance

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin
    Changing the default values of the downsampling options is unsupported.
Sign In or Register to comment.