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 ------------------------------------------------------------------------------------------

Comments

  • ygongygong Member
    edited January 2014

    By the way, our java version is :

    
    [usr@machine path]$ java -version
    java version "1.7.0_45"
    Java(TM) SE Runtime Environment (build 1.7.0_45-b18)
    Java HotSpot(TM) 64-Bit Server VM (build 24.45-b08, mixed mode)
    

    Thanks.

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie

    Hi there,

    I don't think the java version is an issue here; it would crash sooner if it was. It looks like a bug in a calculation. Perhaps @kcibul will be able to help you.

  • ygongygong Member
    edited February 2014

    Hi,

    Is there anybody got any idea about this problem?

    @kcibul @Geraldine_VdAuwer

    Thanks.

  • psanchez820psanchez820 Mexico CityMember

    Hi!

    I have the same issue. I ran a T/N sample pair to which I reduced the reads . I ran the same sample pair of .bam files that had not been reduced and MuTect runs fine. I wonder if that could be the problem?

  • Hi, @psanchez820

    I will run un-reduced reads .bam files again and see whether I got it through. If so, then I believe "reduce reads" maybe an issue.

    But of course, in order to answer this question, we do need MuTect team's respond.

    Thanks for this information.

  • kcibulkcibul Cambridge, MAMember, Broadie, Dev

    MuTect does not work on reduced BAMs -- this was a technology invented to reduce the complexity of BAMs for use in multi-sample germline calling. I'm not sure if this explains your error message, but regardless the recommended use is against un-reduced BAMs.

    If you continue to have this problem with un-reduced BAMs, I would ask that you try the latest build from source in GitHub. Also if you could create a test case from your data (if that's possible) with just the problematic loci, that would allow us to debug the problem.

  • This is a great answer.

    I will try on un-reduced reads and update the result here.

    Thanks for the respond.

  • It seems like it's working now.

    How can I mark this post as "Answered"?

    I didn't see "Did this answered your question? Yes or No" under your post.

    Or I don't really need to do it.

    Thanks.

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