FilterAlignmentArtifacts - Padded span must contain active span

[dansteiert]

Bug Report

Affected tool(s) or class(es)

FilterAlignmentArtifacts
supplied: Variant File, BAM File, Genome, (hg19) --bwa-mem-index-image (from resource bundle (hg38)

Affected version(s)

• [x ] Latest public release version 4.6.1.0 (DockerHub) with Apptainer

Description

I narrowed the issue down to 1000 variants, Identified a rather long insertion (58bp) within it.
By removing this variant, the remaining 999 variants pass, all variants it fails and just the single variant, it passes.

This issue does not always come up, only in a subset of samples, and usually near the end after couple hours of computation.

The insertion in question is:

#CHROM  POS     ID      REF     ALT     QUAL    FILTER  INFO    FORMAT  SAMPLE
Y       28511177        .       C       CACAGCAAAGTCCTGGTTGGGTCAGTGTCATGAATACCGTGGCATCGGCCTGGCAAGG       .       weak_evidence   AS_FilterStatus=weak_evidence;AS_SB_TABLE=2,1|0,1;DP=4;ECNT=1;ECNTH=1;GERMQ=4;MBQ=20,20;MFRL=180,135;MMQ=60,43;MPOS=60;POPAF=7.30;ROQ=93;TLOD=3.58        GT:AD:AF:DP:F1R2:F2R1:FAD:SB    0/1:3,1:0.500:4:0,0:1,1:1,1:2,1,0,1

Log just this variant:

10:58:17.067 INFO  PairHMM - Using the OpenMP multi-threaded AVX-accelerated nati                                                                                                                                                                                                                                            ve PairHMM implementation
10:58:17.067 INFO  ProgressMeter - Starting traversal
10:58:17.068 INFO  ProgressMeter -        Current Locus  Elapsed Minutes    Varia                                                                                                                                                                                                                                            nts Processed  Variants/Minute
10:58:17.084 WARN  FilterAlignmentArtifacts - Error: The requested interval conta                                                                                                                                                                                                                                            ined no data in source VCF files
10:58:17.085 INFO  ProgressMeter -             unmapped              0.0                                                                                                                                                                                                                                                                 0              0.0
10:58:17.086 INFO  ProgressMeter - Traversal complete. Processed 0 total variants                                                                                                                                                                                                                                             in 0.0 minutes.
10:58:17.097 INFO  FilterAlignmentArtifacts - Shutting down engine
[January 14, 2025 at 10:58:17 AM GMT] org.broadinstitute.hellbender.tools.walkers                                                                                                                                                                                                                                            .realignmentfilter.FilterAlignmentArtifacts done. Elapsed time: 0.01 minutes.
Runtime.totalMemory()=104857600
Tool returned:
SUCCESS

Log 999 Variants

11:04:56.862 INFO  PairHMM - Using the OpenMP multi-threaded AVX-accelerated native PairHMM implementation
11:04:56.862 INFO  ProgressMeter - Starting traversal
11:04:56.863 INFO  ProgressMeter -        Current Locus  Elapsed Minutes    Variants Processed  Variants/Minute
11:05:03.047 INFO  ProgressMeter -             unmapped              0.1                    90            873.4
11:05:03.047 INFO  ProgressMeter - Traversal complete. Processed 90 total variants in 0.1 minutes.
11:05:03.081 INFO  FilterAlignmentArtifacts - Shutting down engine
[January 14, 2025 at 11:05:03 AM GMT] org.broadinstitute.hellbender.tools.walkers.realignmentfilter.FilterAlignmentArtifacts done. Elapsed time: 0.12 minutes.
Runtime.totalMemory()=286261248
Tool returned:
SUCCESS

Log 1000 Variants

10:56:20.912 INFO  PairHMM - Using the OpenMP multi-threaded AVX-accelerated nati                                                                                                                                                                                                                                            ve PairHMM implementation
10:56:20.912 INFO  ProgressMeter - Starting traversal
10:56:20.913 INFO  ProgressMeter -        Current Locus  Elapsed Minutes    Varia                                                                                                                                                                                                                                            nts Processed  Variants/Minute
10:57:58.639 INFO  FilterAlignmentArtifacts - Shutting down engine
[January 14, 2025 at 10:57:58 AM GMT] org.broadinstitute.hellbender.tools.walkers                                                                                                                                                                                                                                            .realignmentfilter.FilterAlignmentArtifacts done. Elapsed time: 1.65 minutes.
Runtime.totalMemory()=294649856
java.lang.IllegalStateException: Padded span must contain active span.
        at org.broadinstitute.hellbender.utils.Utils.validate(Utils.java:814)
        at org.broadinstitute.hellbender.engine.AssemblyRegion.<init>(AssemblyRegion.java:109)
        at org.broadinstitute.hellbender.engine.AssemblyRegion.<init>(AssemblyRegion.java:85)
        at org.broadinstitute.hellbender.engine.AssemblyRegion.<init>(AssemblyRegion.java:120)
        at org.broadinstitute.hellbender.tools.walkers.realignmentfilter.FilterAlignmentArtifacts.makeAssemblyRegionFromVariantReads(FilterAlignmentArtifacts.java:281)
        at org.broadinstitute.hellbender.tools.walkers.realignmentfilter.FilterAlignmentArtifacts.apply(FilterAlignmentArtifacts.java:213)
        at org.broadinstitute.hellbender.engine.MultiVariantWalkerGroupedOnStart.apply(MultiVariantWalkerGroupedOnStart.java:133)
        at org.broadinstitute.hellbender.engine.MultiVariantWalkerGroupedOnStart.afterTraverse(MultiVariantWalkerGroupedOnStart.java:193)
        at org.broadinstitute.hellbender.engine.MultiVariantWalkerGroupedOnStart.traverse(MultiVariantWalkerGroupedOnStart.java:166)
        at org.broadinstitute.hellbender.engine.GATKTool.doWork(GATKTool.java:1119)
        at org.broadinstitute.hellbender.cmdline.CommandLineProgram.runTool(CommandLineProgram.java:150)
        at org.broadinstitute.hellbender.cmdline.CommandLineProgram.instanceMainPostParseArgs(CommandLineProgram.java:203)
        at org.broadinstitute.hellbender.cmdline.CommandLineProgram.instanceMain(CommandLineProgram.java:222)
        at org.broadinstitute.hellbender.Main.runCommandLineProgram(Main.java:166                                                                                                                                                                                                                                            )
        at org.broadinstitute.hellbender.Main.mainEntry(Main.java:209)
        at org.broadinstitute.hellbender.Main.main(Main.java:306)

entries from the genome dict:

@SQ     SN:21   LN:48129895     M5:** UR:file:**
@SQ     SN:22   LN:51304566     M5:** UR:file:**
@SQ     SN:X    LN:155270560    M5:** UR:file:**
@SQ     SN:Y    LN:59373566     M5:** UR:file:**
@SQ     SN:MT   LN:16569        M5:** UR:file:**