GATK 2.8.1 Unified Genotyper "Null alleles are not supported"

Dear all,

all my GATK 2.8.1 UG jobs crash with the "Null alleles are not supported" error message.
It works fine with 2.7.4 (more precisely the nightly release version as of November 28) but this error message kills all my jobs right now with the just released 2.8.1 version. Based on the traces, it looks like an indel calling issue.

It's multisample calling, with reduced reads format. The issue may come from the fact that a handful of BAM files have been reduced with older versions of GATK (something I am currently fixing, but it takes time). The fact that the issue is brand new to 2.8.1 suggests something different though but I can't be sure. Full error message below.

Any idea?

V

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

java.lang.IllegalArgumentException: Null alleles are not supported
at org.broadinstitute.variant.variantcontext.Allele.(Allele.java:117)
at org.broadinstitute.sting.utils.haplotype.Haplotype.(Haplotype.java:61)
at org.broadinstitute.sting.gatk.walkers.indels.PairHMMIndelErrorModel.trimHaplotypes(PairHMMIndelErrorModel.java:235)
at org.broadinstitute.sting.gatk.walkers.indels.PairHMMIndelErrorModel.computeGeneralReadHaplotypeLikelihoods(PairHMMIndelErrorModel.java:438)
at org.broadinstitute.sting.gatk.walkers.indels.PairHMMIndelErrorModel.computeDiploidReadHaplotypeLikelihoods(PairHMMIndelErrorModel.java:251)
at org.broadinstitute.sting.gatk.walkers.genotyper.IndelGenotypeLikelihoodsCalculationModel.getLikelihoods(IndelGenotypeLikelihoodsCalculationModel.java:149)
at org.broadinstitute.sting.gatk.walkers.genotyper.UnifiedGenotyperEngine.calculateLikelihoods(UnifiedGenotyperEngine.java:331)
at org.broadinstitute.sting.gatk.walkers.genotyper.UnifiedGenotyperEngine.calculateLikelihoodsAndGenotypes(UnifiedGenotyperEngine.java:232)
at org.broadinstitute.sting.gatk.walkers.genotyper.UnifiedGenotyper.map(UnifiedGenotyper.java:367)
at org.broadinstitute.sting.gatk.walkers.genotyper.UnifiedGenotyper.map(UnifiedGenotyper.java:143)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano$TraverseLociMap.apply(TraverseLociNano.java:267)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano$TraverseLociMap.apply(TraverseLociNano.java:255)
at org.broadinstitute.sting.utils.nanoScheduler.NanoScheduler.executeSingleThreaded(NanoScheduler.java:274)
at org.broadinstitute.sting.utils.nanoScheduler.NanoScheduler.execute(NanoScheduler.java:245)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:144)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:92)
at org.broadinstitute.sting.gatk.traversals.TraverseLociNano.traverse(TraverseLociNano.java:48)
at org.broadinstitute.sting.gatk.executive.ShardTraverser.call(ShardTraverser.java:98)
at java.util.concurrent.FutureTask$Sync.innerRun(FutureTask.java:334)
at java.util.concurrent.FutureTask.run(FutureTask.java:166)
at java.util.concurrent.ThreadPoolExecutor.runWorker(ThreadPoolExecutor.java:1145)
at java.util.concurrent.ThreadPoolExecutor$Worker.run(ThreadPoolExecutor.java:615)
at java.lang.Thread.run(Thread.java:724)

ERROR ------------------------------------------------------------------------------------------
ERROR A GATK RUNTIME ERROR has occurred (version 2.8-1-g932cd3a):
ERROR
ERROR This might be a bug. Please check the documentation guide to see if this is a known problem.
ERROR If not, please post the error message, 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: Null alleles are not supported
ERROR ------------------------------------------------------------------------------------------

Best Answer

Answers

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Hi Vincent,

    This might be related to a bugfix we put in just before the release. Could you please upload a test snippet so we can debug locally?

  • vplagnolvplagnol Member

    I'll try but it's not going to be super obvious to do: the program runs for a while before crashing and I have only tried on the full set of exomes (~ 2K of them). But maybe it will also crash with smaller numbers, perhaps even single sample if we are lucky. I'll experiment and get back to you, but it may take a bit of time to come up with something that does not involve Tbs of data.

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Ah, well let's hope for a quick crash then ;)

    Seriously though, sorry for the inconvenience.

  • vplagnolvplagnol Member

    If you give me the nightly release data before/after the bug fix, I can probably at least confirm that it happens as a consequence of that.

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    The fix went into the dev trunk on the Monday after Thanksgiving weekend, Dec. 2. So I think you would want to test the nightly for 12/2 vs. 12/3.

  • dcittarodcittaro Member

    @vplagnol: did the update resolve the issue? I'm having the very exact one. Also, GATK-2.8-1 is still the latest version available

  • dcittarodcittaro Member

    FYI version nightly-2013-12-12-g9981965 doesn't resolve the issue. Is there a way I can download the last version of 2.7 series?

  • vplagnolvplagnol Member

    @dcittaro I haven't to create a simple bug report yet. I am on it though, if someone (you?) manages to pinpoint the pbm I am sure the GATK team will fix it quickly.

    I can't find an easy way to download the earlier versions but I am sure it's somewhere on the website (and If you are desperate I can send you a version prior to the "big fix", but there must be an earlier version available somewhere).

  • vplagnolvplagnol Member
    edited December 2013

    OK bug report uploaded, it should be easily reproducible. I had to include a good number of BAM files though to make the crash happen. The compressed file is
    Plagnol_debug_null_alleles.tar.gz

    Geraldine, please let me know if you guys can use it without issues.

    Thanks again.

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Hi Vincent,

    Thanks for the well-organized bug report; I was able to reproduce your bug without difficulty. I'll let you know when we know more about what's going on here.

  • vplagnolvplagnol Member

    Thanks Geraldine once again, looking forward to seeing it working.
    Just a question I have asked before, has there been changes recently in the reduced reads module? It matters because I need to know whether updating to that bug fixed GATK version also means updating my reduced reads BAMs.

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Nope, no changes.

  • DonbyDonby Member
    edited February 2014

    I have met the same problems. But when using the lasted versions of GATK(nightly-2014-02-03-gc6765ad), a new problem came accross and the error is: MESSAGE: HAPLOTYPE_MAX_LENGTH must be > 0 but got 0. The dataset i used was RNA sequencing data. Hope you can help me!

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    Hi @Donby,

    We haven't seen that before, it might be an RNA-specific issue. If so that's not something we can take time to fix right now because it's an unsupported usage of the tools. However we have some new RNAseq-specific tools coming out in the new version 3.0 in a couple of weeks. I would recommend you wait for the new tools to process your data, if you can.

  • DonbyDonby Member

    Thanks Geraldine. Looking forward to the new version 3.0

  • hashishhashish SaudiMember

    @Geraldine_VdAuwera said:
    Hi @Donby,

    We haven't seen that before, it might be an RNA-specific issue. If so that's not something we can take time to fix right now because it's an unsupported usage of the tools. However we have some new RNAseq-specific tools coming out in the new version 3.0 in a couple of weeks. I would recommend you wait for the new tools to process your data, if you can.

    Hello, I have the same error that Donby mentioned: "MESSAGE: HAPLOTYPE_MAX_LENGTH must be > 0 but got 0" but I'm using DNA sequencing data and GATK 3.5

  • Geraldine_VdAuweraGeraldine_VdAuwera Cambridge, MAMember, Administrator, Broadie admin

    @hashish What was your command line?

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