Error Cumulative probability function returned NaN for argument 0.975 p = 0.975 running MuTect

ygongygong Member
edited January 2014 in Ask the GATK team

Hello MuTect Team,

I encountered a error when running MuTect on our server for our tumor and normal pair data. If anyone can help me about his, it will be greatly appreciated.

I black out the file path by " ** " for security reason.

The tumor and normal BAM files are aligned against ucsc.hg19.fasta and all the references are using hg19 from GATK 2.8 resource bundle.

  • dbSNP: dbsnp_137.hg19.vcf
  • reference: ucsc.hg19.fasta
  • COSMIC:

    The cosmic file is generated by myself by using the following command:

    perl **/GenomeAnalysisTK-2.8-1/liftOverVCF.pl -vcf 2.8/b37_cosmic_v54_120711.vcf -chain b37tohg19.chain -out hg19_cosmic_v54.vcf -newRef ucsc.hg19 -oldRef 2.8/human_g1k_v37 -gatk **/GenomeAnalysisTK-2.8-1/

The command I run the MuTect is:

java -jar -Xmx16g **/muTect-1.1.4/muTect-1.1.4.jar --analysis_type MuTect --reference_sequence **/ucsc.hg19.fasta --cosmic **/hg19_cosmic_v54.vcf --dbsnp **/dbsnp_137.hg19.vcf --input_file:tumor **/ReduceReads_P1T.bam --input_file:normal **/ReduceReads_P1N.bam --out **/MuTect_P1.out --coverage_file MT_coverage_P1.txt

The log message is as follows:

INFO 13:04:40,315 HelpFormatter - ---------------------------------------------------------------------------------
INFO 13:04:40,317 HelpFormatter - The Genome Analysis Toolkit (GATK) v2.2-25-g2a68eab, Compiled 2012/11/08 10:30:02
INFO 13:04:40,317 HelpFormatter - Copyright (c) 2010 The Broad Institute
INFO 13:04:40,317 HelpFormatter - For support and documentation go to http://www.broadinstitute.org/gatk
INFO 13:04:40,321 HelpFormatter - Program Args: --analysis_type MuTect --reference_sequence **/ucsc.hg19.fasta --cosmic **/hg19_cosmic_v54.vcf --dbsnp **/dbsnp_137.hg19.vcf --input_file:tumor **/ReduceReads_P1T.bam --input_file:normal **/ReduceReads_P1N.bam --out **/MuTect_P1.out --coverage_file MT_coverage_P1.txt
INFO 13:04:40,321 HelpFormatter - Date/Time: 2014/01/14 13:04:40
INFO 13:04:40,321 HelpFormatter - ---------------------------------------------------------------------------------
INFO 13:04:40,321 HelpFormatter - ---------------------------------------------------------------------------------
INFO 13:04:40,341 ArgumentTypeDescriptor - Dynamically determined type of **/dbsnp_137.hg19.vcf to be VCF
INFO 13:04:40,346 ArgumentTypeDescriptor - Dynamically determined type of **/hg19_cosmic_v54.vcf to be VCF
INFO 13:04:40,353 GenomeAnalysisEngine - Strictness is SILENT
INFO 13:04:40,414 GenomeAnalysisEngine - Downsampling Settings: Method: BY_SAMPLE Target Coverage: 1000
INFO 13:04:40,420 SAMDataSource$SAMReaders - Initializing SAMRecords in serial
INFO 13:04:40,449 SAMDataSource$SAMReaders - Done initializing BAM readers: total time 0.03
INFO 13:04:40,466 RMDTrackBuilder - Loading Tribble index from disk for file **/dbsnp_137.hg19.vcf
INFO 13:04:40,585 RMDTrackBuilder - Loading Tribble index from disk for file **/hg19_cosmic_v54.vcf
INFO 13:04:40,643 ProgressMeter - [INITIALIZATION COMPLETE; STARTING PROCESSING]
INFO 13:04:40,643 ProgressMeter - Location processed.sites runtime per.1M.sites completed total.runtime remaining
Error processing chrM:117
org.apache.commons.math.FunctionEvaluationException: Cumulative probability function returned NaN for argument 0.975 p = 0.975
at org.apache.commons.math.distribution.AbstractContinuousDistribution$1.value(AbstractContinuousDistribution.java:107)
at org.apache.commons.math.analysis.solvers.BrentSolver.solve(BrentSolver.java:388)
at org.apache.commons.math.analysis.solvers.BrentSolver.solve(BrentSolver.java:250)
at org.apache.commons.math.analysis.solvers.UnivariateRealSolverUtils.solve(UnivariateRealSolverUtils.java:82)
at org.apache.commons.math.distribution.AbstractContinuousDistribution.inverseCumulativeProbability(AbstractContinuousDistribution.java:138)
at org.apache.commons.math.distribution.BetaDistributionImpl.inverseCumulativeProbability(BetaDistributionImpl.java:176)
at org.broadinstitute.cga.tools.gatk.walkers.cancer.mutect.MuTect.map(MuTect.java:454)
at org.broadinstitute.cga.tools.gatk.walkers.cancer.mutect.MuTect.map(MuTect.java:34)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano$TraverseLociMap.apply(TraverseLociNano.java:243)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano$TraverseLociMap.apply(TraverseLociNano.java:231)
at org.broadinstitute.sting.utils.nanoScheduler.NanoScheduler.executeSingleThreaded(NanoScheduler.java:287)
at org.broadinstitute.sting.utils.nanoScheduler.NanoScheduler.execute(NanoScheduler.java:252)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:120)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:67)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:23)
at org.broadinstitute.sting.gatk.executive.LinearMicroScheduler.execute(LinearMicroScheduler.java:74)
at org.broadinstitute.sting.gatk.GenomeAnalysisEngine.execute(GenomeAnalysisEngine.java:281)
at org.broadinstitute.sting.gatk.CommandLineExecutable.execute(CommandLineExecutable.java:113)
at org.broadinstitute.sting.commandline.CommandLineProgram.start(CommandLineProgram.java:236)
at org.broadinstitute.sting.commandline.CommandLineProgram.start(CommandLineProgram.java:146)
at org.broadinstitute.sting.gatk.CommandLineGATK.main(CommandLineGATK.java:93)
INFO 13:04:42,505 HttpMethodDirector - I/O exception (java.net.ConnectException) caught when processing request: Connection refused
INFO 13:04:42,506 HttpMethodDirector - Retrying request
INFO 13:04:42,511 HttpMethodDirector - I/O exception (java.net.ConnectException) caught when processing request: Connection refused
INFO 13:04:42,511 HttpMethodDirector - Retrying request
INFO 13:04:42,515 HttpMethodDirector - I/O exception (java.net.ConnectException) caught when processing request: Connection refused
INFO 13:04:42,516 HttpMethodDirector - Retrying request
INFO 13:04:42,518 HttpMethodDirector - I/O exception (java.net.ConnectException) caught when processing request: Connection refused
INFO 13:04:42,519 HttpMethodDirector - Retrying request
INFO 13:04:42,523 HttpMethodDirector - I/O exception (java.net.ConnectException) caught when processing request: Connection refused
INFO 13:04:42,524 HttpMethodDirector - Retrying request

ERROR ------------------------------------------------------------------------------------------
ERROR stack trace

java.lang.RuntimeException: org.apache.commons.math.FunctionEvaluationException: Cumulative probability function returned NaN for argument 0.975 p = 0.975
at org.broadinstitute.cga.tools.gatk.walkers.cancer.mutect.MuTect.map(MuTect.java:712)
at org.broadinstitute.cga.tools.gatk.walkers.cancer.mutect.MuTect.map(MuTect.java:34)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano$TraverseLociMap.apply(TraverseLociNano.java:243)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano$TraverseLociMap.apply(TraverseLociNano.java:231)
at org.broadinstitute.sting.utils.nanoScheduler.NanoScheduler.executeSingleThreaded(NanoScheduler.java:287)
at org.broadinstitute.sting.utils.nanoScheduler.NanoScheduler.execute(NanoScheduler.java:252)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:120)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:67)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:23)
at org.broadinstitute.sting.gatk.executive.LinearMicroScheduler.execute(LinearMicroScheduler.java:74)
at org.broadinstitute.sting.gatk.GenomeAnalysisEngine.execute(GenomeAnalysisEngine.java:281)
at org.broadinstitute.sting.gatk.CommandLineExecutable.execute(CommandLineExecutable.java:113)
at org.broadinstitute.sting.commandline.CommandLineProgram.start(CommandLineProgram.java:236)
at org.broadinstitute.sting.commandline.CommandLineProgram.start(CommandLineProgram.java:146)
at org.broadinstitute.sting.gatk.CommandLineGATK.main(CommandLineGATK.java:93)
Caused by: org.apache.commons.math.FunctionEvaluationException: Cumulative probability function returned NaN for argument 0.975 p = 0.975
at org.apache.commons.math.distribution.AbstractContinuousDistribution$1.value(AbstractContinuousDistribution.java:107)
at org.apache.commons.math.analysis.solvers.BrentSolver.solve(BrentSolver.java:388)
at org.apache.commons.math.analysis.solvers.BrentSolver.solve(BrentSolver.java:250)
at org.apache.commons.math.analysis.solvers.UnivariateRealSolverUtils.solve(UnivariateRealSolverUtils.java:82)
at org.apache.commons.math.distribution.AbstractContinuousDistribution.inverseCumulativeProbability(AbstractContinuousDistribution.java:138)
at org.apache.commons.math.distribution.BetaDistributionImpl.inverseCumulativeProbability(BetaDistributionImpl.java:176)
at org.broadinstitute.cga.tools.gatk.walkers.cancer.mutect.MuTect.map(MuTect.java:454)
... 14 more

ERROR ------------------------------------------------------------------------------------------
ERROR A GATK RUNTIME ERROR has occurred (version 2.2-25-g2a68eab):
ERROR
ERROR Please visit the wiki to see if this is a known problem
ERROR If not, please post the error, with stack trace, to the GATK forum
ERROR Visit our website and forum for extensive documentation and answers to
ERROR commonly asked questions http://www.broadinstitute.org/gatk
ERROR
ERROR MESSAGE: org.apache.commons.math.FunctionEvaluationException: Cumulative probability function returned NaN for argument 0.975 p = 0.975
ERROR ------------------------------------------------------------------------------------------

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