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Mutect2 processing stops with java.nio.BufferUnderflowException?

Got this java.nio.BufferUnderflowException manyh hours into processing a tumor-normal sample with Mutect2. A more helpful error message would have been appreciated:

08:15:10.763 INFO  ProgressMeter -       chr7:158995850           4925.5               9505510           1929.9
08:15:21.370 INFO  ProgressMeter -       chr7:159062569           4925.6               9505940           1929.9
08:15:31.442 INFO  ProgressMeter -       chr7:159111130           4925.8               9506280           1929.9
08:15:41.507 INFO  ProgressMeter -       chr7:159156160           4926.0               9506580           1929.9
08:15:51.597 INFO  ProgressMeter -       chr7:159202084           4926.1               9506870           1929.9
08:16:01.814 INFO  ProgressMeter -       chr7:159252198           4926.3               9507190           1929.9
08:16:12.104 INFO  ProgressMeter -       chr7:159301154           4926.5               9507500           1929.9
08:16:23.526 INFO  VectorLoglessPairHMM - Time spent in setup for JNI call : 316.52971563700004
08:16:23.526 INFO  PairHMM - Total compute time in PairHMM computeLogLikelihoods() : 15575.274527761001
08:16:23.532 INFO  SmithWatermanAligner - Total compute time in java Smith-Waterman : 39442.02 sec
INFO    2019-03-22 08:16:27     SortingCollection       Creating merging iterator from 28 files
08:19:07.238 INFO  Mutect2 - Shutting down engine
[March 22, 2019 8:19:07 AM UTC] org.broadinstitute.hellbender.tools.walkers.mutect.Mutect2 done. Elapsed time: 4,929.47 minutes.
Runtime.totalMemory()=16488333312
java.nio.BufferUnderflowException
        at java.nio.Buffer.nextGetIndex(Buffer.java:506)
        at java.nio.DirectByteBuffer.getInt(DirectByteBuffer.java:681)
        at htsjdk.samtools.AbstractBAMFileIndex$MemoryMappedFileBuffer.readInteger(AbstractBAMFileIndex.java:498)
        at htsjdk.samtools.AbstractBAMFileIndex.readInteger(AbstractBAMFileIndex.java:442)
        at htsjdk.samtools.AbstractBAMFileIndex.query(AbstractBAMFileIndex.java:279)
        at htsjdk.samtools.DiskBasedBAMFileIndex.getSpanOverlapping(DiskBasedBAMFileIndex.java:61)
        at htsjdk.samtools.BAMFileReader.getFileSpan(BAMFileReader.java:898)
        at htsjdk.samtools.BAMFileReader.createIndexIterator(BAMFileReader.java:915)
        at htsjdk.samtools.BAMFileReader.query(BAMFileReader.java:575)
        at htsjdk.samtools.SamReader$PrimitiveSamReaderToSamReaderAdapter.query(SamReader.java:528)
        at htsjdk.samtools.SamReader$PrimitiveSamReaderToSamReaderAdapter.queryOverlapping(SamReader.java:400)
        at org.broadinstitute.hellbender.utils.iterators.SamReaderQueryingIterator.loadNextIterator(SamReaderQueryingIterator.java:125)
        at org.broadinstitute.hellbender.utils.iterators.SamReaderQueryingIterator.(SamReaderQueryingIterator.java:66)
        at org.broadinstitute.hellbender.engine.ReadsDataSource.prepareIteratorsForTraversal(ReadsDataSource.java:404)
        at org.broadinstitute.hellbender.engine.ReadsDataSource.iterator(ReadsDataSource.java:330)
        at org.broadinstitute.hellbender.engine.MultiIntervalLocalReadShard.iterator(MultiIntervalLocalReadShard.java:134)
        at org.broadinstitute.hellbender.engine.AssemblyRegionIterator.(AssemblyRegionIterator.java:109)
        at org.broadinstitute.hellbender.engine.AssemblyRegionWalker.processReadShard(AssemblyRegionWalker.java:282)
        at org.broadinstitute.hellbender.engine.AssemblyRegionWalker.traverse(AssemblyRegionWalker.java:267)
        at org.broadinstitute.hellbender.engine.GATKTool.doWork(GATKTool.java:966)
        at org.broadinstitute.hellbender.cmdline.CommandLineProgram.runTool(CommandLineProgram.java:139)
        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)
Using GATK jar /gatk/gatk-package-4.0.11.0-local.jar



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Answers

  • bhanuGandhambhanuGandham Cambridge MAMember, Administrator, Broadie, Moderator admin

    Hi @registered_user

    Please post the exact commands you used and the version of gatk.
    Also, if you are not using the latest version GATK4.1.1.0, then please use that see if the problem persists.

  • "Using GATK jar /gatk/gatk-package-4.0.11.0-local.jar"
    I think this issue has to do with server load and disk I/O response times. It's too hard to try to replicate. In general, I've seen lots of different Java exceptions with Mutect2 that are not very informative to the user. If I can make a wish it would be that somebody would go through possible errors/ exceptions and make sure the error messages would be more useful in trying to pinpoint the problem.

  • bhanuGandhambhanuGandham Cambridge MAMember, Administrator, Broadie, Moderator admin

    HI @registered_user

    The Mutect2 team is continually working on better/informative ways it handles errors. Thank you for bringing this to our attention and @bshifaw will relay this to the dev team.

    In the mean time if you have other questions or concerns please reach out to us.

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