FilterMutectCalls fails under mitochondria mode

[elcortegano]

I'm using GATK 4.2.1.0-0 tool Mutect2 to call mutations in a mitochondrion genome, and later processing the VCFs with FilterMutectCalls enabling as well the mitochondria mode (--mitochondria-mode true).

For some reason, this results in some of the VCFs to return the following error:

java.lang.IllegalArgumentException: log10p: Log10-probability must be 0 or less
at org.broadinstitute.hellbender.utils.Utils.validateArg(Utils.java:798)
at org.broadinstitute.hellbender.utils.MathUtils.log10BinomialProbability(MathUtils.java:646)
at org.broadinstitute.hellbender.utils.MathUtils.binomialProbability(MathUtils.java:639)
at org.broadinstitute.hellbender.tools.walkers.mutect.clustering.SomaticClusteringModel.lambda$calculateQuantileBackgroundResponsibilities$10(SomaticClusteringModel.java:271)
at org.broadinstitute.hellbender.utils.MathUtils.applyToArray(MathUtils.java:1035)
at org.broadinstitute.hellbender.tools.walkers.mutect.clustering.SomaticClusteringModel.calculateQuantileBackgroundResponsibilities(SomaticClusteringModel.java:271)
at org.broadinstitute.hellbender.tools.walkers.mutect.clustering.SomaticClusteringModel.initializeClusters(SomaticClusteringModel.java:165)
at org.broadinstitute.hellbender.tools.walkers.mutect.clustering.SomaticClusteringModel.learnAndClearAccumulatedData(SomaticClusteringModel.java:325)
at org.broadinstitute.hellbender.tools.walkers.mutect.filtering.Mutect2FilteringEngine.learnParameters(Mutect2FilteringEngine.java:153)
at org.broadinstitute.hellbender.tools.walkers.mutect.filtering.FilterMutectCalls.afterNthPass(FilterMutectCalls.java:165)
at org.broadinstitute.hellbender.engine.MultiplePassVariantWalker.traverse(MultiplePassVariantWalker.java:44)
at org.broadinstitute.hellbender.engine.GATKTool.doWork(GATKTool.java:1085)
at org.broadinstitute.hellbender.cmdline.CommandLineProgram.runTool(CommandLineProgram.java:140)
at org.broadinstitute.hellbender.cmdline.CommandLineProgram.instanceMainPostParseArgs(CommandLineProgram.java:192)
at org.broadinstitute.hellbender.cmdline.CommandLineProgram.instanceMain(CommandLineProgram.java:211)
at org.broadinstitute.hellbender.Main.runCommandLineProgram(Main.java:160)
at org.broadinstitute.hellbender.Main.mainEntry(Main.java:203)
at org.broadinstitute.hellbender.Main.main(Main.java:289)

For those files experiencing the error, it disappears when disabling the mitochondria mode for FilterMutectCalls.

I wonder how this problem could be solved so that all VCFs can be filtering in a consistent way, enabling the mitochondria mode. I am happy to share the VCF and reference sequence used it that helps reproducing/solving the issue.

Thank you,
Eugenio

[meganshand]

Hi @elcortegano, could you please provide a minimal example VCF and reference that has this issue?

[elcortegano]

Hi @meganshand , sure, please find those attached below.

files.zip

GATK was run with:

gatk FilterMutectCalls --mitochondria-mode true -V FVB_4.mutect2.vcf -O test.vcf -R NC_005089.1.fa

[meganshand]

@elcortegano Thank you for reporting this and providing the test data! The fix was just merged so the next release of GATK should resolve this issue for you.