Variant Annotator annotations

vsravi

I am trying to understand how Variant Annotator functions. I took the vcf file from the output of UnifiedGenotyper and ran Variant Annotator with the same .bam and .bed files I used for running UnifiedGenotyper. I expected that all the calculations in the INFO field will remain the same, since I am using the same input files. However, I find that some fields have different values. Here is an example: UnifiedGenotyper output:

chr22   30094366        .       G       A       172.01  .       AC=1;AF=0.500;AN=2;BaseQRankSum=3.182;DP=244;DS;Dels=0.00;FS=0.000;HaplotypeScore=118.5897;MLEAC=1;MLEAF=0.500;MQ=43.29;MQ0=0;MQRankSum=-0.049;QD=0.70;ReadPosRankSum=1.428;SB=-6.201e+01        GT:AD:DP:GQ:PL  0/1:220,19:244:99:202,0,2693 

VariantAnnotator output:

chr22   30094366        .       G       A       172.01  .       ABHet=0.923;AC=1;AF=0.500;AN=2;BaseQRankSum=3.182;DP=993;DS;Dels=0.00;FS=0.000;HaplotypeScore=454.8386;MLEAC=1;MLEAF=0.500;MQ=43.29;MQ0=0;MQ0Fraction=0.0000;MQRankSum=-0.378;OND=0.034;QD=0.17;ReadPosRankSum=-4.859;SB=-6.201e+01      GT:AD:DP:GQ:PL  0/1:220,19:244:99:202,0,2693

I am running GATKLite 2.1. Notice the DP in the info field has a different value. HaplotypeScore, QD, MQRankSum, etc have different values as well. Am I doing anything wrong? Shouldn't these values be the same when I recalculate these fields using VariantAnnotator?

Geraldine_VdAuwera

The Unified Genotyper has a different default downsampling value compared to other tools like VariantAnnotator (which use the engine's default downsampling setting). So when you run VariantAnnotator, you're looking at more reads than with the UG, which changes some of the annotation values accordingly.

Geraldine_VdAuwera

These topics have been addressed more or less directly in the following articles:

http://gatkforums.broadinstitute.org/discussion/1323/sampling-and-filtering-reads http://gatkforums.broadinstitute.org/discussion/1457/recommended-filters-for-unifiedgenotyper http://gatkforums.broadinstitute.org/discussion/1237/using-the-unified-genotyper

Unfortunately right now our documentation system isn't configured to emit that information concisely in one place. We're aware that this is not an ideal situation and we plan to rectify it, but it might take a while. In the meantime the most reliable way to find out is to look it up in the codebase, although this is admittedly not really straightforward if you are not comfortable with Java code.

Geraldine_VdAuwera

Also, the two apply different read filters by default, which may account for part of the differences as well.

vsravi

Thanks for the clarification. Is there a way to find out what are all the read filters and default thresholds applied in each program?