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Haplotypecaller 4.5.2.0 --alleles unexpected output #7741

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GATKSupportTeam opened this issue Mar 29, 2022 · 0 comments · Fixed by #7740
Closed

Haplotypecaller 4.5.2.0 --alleles unexpected output #7741

GATKSupportTeam opened this issue Mar 29, 2022 · 0 comments · Fixed by #7740

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@GATKSupportTeam
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James has a branch already that seems to solve this edge case.

This request was created from a contribution made by Geert Vandeweyer on March 13, 2022 08:49 UTC.

Link: https://gatk.broadinstitute.org/hc/en-us/community/posts/4664460343195-Haplotypecaller-4-5-2-0-alleles-unexpected-output

--

  • Output VCF file contains entries like below when '--alleles' is used: 

chr5    125894866       .       C       T       Infinity        .       AC=0;AF=0.00;AN=2;DP=31;ExcessHet=0.0000;FS=0.000;MLEAC=0;MLEAF=0.00;MQ=60.00;SOR=0.188 GT:AD:DP:GP:GQ:PG:PL    0/0:30,0:30:0,124.77,167.78:99:0,34.77,37.78:0,90,130

chr5    125895079       .       A       .       94.78   .       AN=2;DP=37;MQ=60.00     GT:AD:DP        0/0:37:37

chr5    125895106       .       G       .       73.78   .       AN=2;DP=28;MQ=60.00     GT:AD:DP        0/0:28:28

chr5    125895113       .       G       .       68.78   .       AN=2;DP=25;MQ=60.00     GT:AD:DP        0/0:25:25

Position 125894866 is present in the --alleles file, and is genotyped correctrly as homozygous reference in the current sample. The following three positions are not present in the --alleles file, and do not contain an ALT allele in the output file ( dot for ALT).   without '--alleles', these positions are not outputted. 

Is this expected behaviour, and if so, why are they emitted ?

notes :

- same output is observed without threading ,

- same output is observed without dragen mode. 

-  --alleles is taken from a normal HC run. 

-  roughly the same heterozygous calls & hom.ALT calls are made with/without --alleles (which is expected behaviour)

=======================

REQUIRED for all errors and issues:

a) GATK version used: 4.2.5.0

b) Exact command used:

gatk --java-options "-Djava.io.tmpdir=/tmp -Xmx3g" HaplotypeCaller \

  -R /home/gvandeweyer/elprep_streaming/reference/hg19.fasta \

  -I /home/gvandeweyer/elprep_streaming/results/wesep-229191-f.bam \

  -O results/wesep-229191-f.vcf \

  --alleles affected_alleles.vcf \

  -L 0005-scattered.interval_list \

  -bamout results/wesep-229191-f.variants.bam \

  -G StandardAnnotation -G StandardHCAnnotation \

  --dragen-mode \

  --dragstr-params-path /home/gvandeweyer/elprep_streaming/results/wesep-229191-f.bam.params \

  --native-pair-hmm-threads 2

 

c) Entire program log:

(ELPREP) gvandeweyer@ngsvm-pipelines:~/elprep_streaming/VariantCalling_Test/scattered$ gatk --java-options "-Djava.io.tmpdir=/tmp -Xmx3g" HaplotypeCaller    -R /home/gvandeweyer/elprep_streaming/reference/hg19.fasta    -I /home/gvandeweyer/elprep_streaming/results/wesep-

229191-f.bam    -O results/wesep-229191-f.vcf    --alleles ../wesid-226998-m.haplotypecaller.final.vcf.gz -L 0005-scattered.interval_list    -bamout results/wesep-229191-f.variants.bam    -G StandardAnnotation -G StandardHCAnnotation    --dragen-mode    --dragstr-params-

path /home/gvandeweyer/elprep_streaming/results/wesep-229191-f.bam.params 2>&1 | tee Runtime.log.txt

Using GATK jar /home/gvandeweyer/miniconda3/envs/ELPREP/share/gatk4-4.2.5.0-0/gatk-package-4.2.5.0-local.jar

Running:

   java -Dsamjdk.use_async_io_read_samtools=false -Dsamjdk.use_async_io_write_samtools=true -Dsamjdk.use_async_io_write_tribble=false -Dsamjdk.compression_level=2 -Djava.io.tmpdir=/tmp -Xmx3g -jar /home/gvandeweyer/miniconda3/envs/ELPREP/share/gatk4-4.2.5.0-0/gatk-packa

ge-4.2.5.0-local.jar HaplotypeCaller -R /home/gvandeweyer/elprep_streaming/reference/hg19.fasta -I /home/gvandeweyer/elprep_streaming/results/wesep-229191-f.bam -O results/wesep-229191-f.vcf --alleles ../wesid-226998-m.haplotypecaller.final.vcf.gz -L 0005-scattered.inter

val_list -bamout results/wesep-229191-f.variants.bam -G StandardAnnotation -G StandardHCAnnotation --dragen-mode --dragstr-params-path /home/gvandeweyer/elprep_streaming/results/wesep-229191-f.bam.params

22:06:39.332 WARN  GATKAnnotationPluginDescriptor - Redundant enabled annotation group (StandardAnnotation) is enabled for this tool by default

22:06:39.337 WARN  GATKAnnotationPluginDescriptor - Redundant enabled annotation group (StandardHCAnnotation) is enabled for this tool by default

22:06:39.383 INFO  NativeLibraryLoader - Loading libgkl_compression.so from jar:file:/home/gvandeweyer/miniconda3/envs/ELPREP/share/gatk4-4.2.5.0-0/gatk-package-4.2.5.0-local.jar!/com/intel/gkl/native/libgkl_compression.so

Mar 12, 2022 10:06:39 PM shaded.cloud_nio.com.google.auth.oauth2.ComputeEngineCredentials runningOnComputeEngine

INFO: Failed to detect whether we are running on Google Compute Engine.

22:06:39.543 INFO  HaplotypeCaller - ------------------------------------------------------------

22:06:39.543 INFO  HaplotypeCaller - The Genome Analysis Toolkit (GATK) v4.2.5.0

22:06:39.543 INFO  HaplotypeCaller - For support and documentation go to https://software.broadinstitute.org/gatk/

22:06:39.543 INFO  HaplotypeCaller - Executing as [email protected] on Linux v4.4.0-210-generic amd64

22:06:39.543 INFO  HaplotypeCaller - Java runtime: OpenJDK 64-Bit Server VM v1.8.0_312-b07

22:06:39.544 INFO  HaplotypeCaller - Start Date/Time: March 12, 2022 10:06:39 PM CET

22:06:39.544 INFO  HaplotypeCaller - ------------------------------------------------------------

22:06:39.544 INFO  HaplotypeCaller - ------------------------------------------------------------

22:06:39.544 INFO  HaplotypeCaller - HTSJDK Version: 2.24.1

22:06:39.544 INFO  HaplotypeCaller - Picard Version: 2.25.4

22:06:39.544 INFO  HaplotypeCaller - Built for Spark Version: 2.4.5

22:06:39.544 INFO  HaplotypeCaller - HTSJDK Defaults.COMPRESSION_LEVEL : 2

22:06:39.545 INFO  HaplotypeCaller - HTSJDK Defaults.USE_ASYNC_IO_READ_FOR_SAMTOOLS : false

22:06:39.545 INFO  HaplotypeCaller - HTSJDK Defaults.USE_ASYNC_IO_WRITE_FOR_SAMTOOLS : true

22:06:39.545 INFO  HaplotypeCaller - HTSJDK Defaults.USE_ASYNC_IO_WRITE_FOR_TRIBBLE : false

22:06:39.545 INFO  HaplotypeCaller - Deflater: IntelDeflater

22:06:39.545 INFO  HaplotypeCaller - Inflater: IntelInflater

22:06:39.545 INFO  HaplotypeCaller - GCS max retries/reopens: 20

22:06:39.545 INFO  HaplotypeCaller - Requester pays: disabled

22:06:39.545 INFO  HaplotypeCaller - Initializing engine

22:06:40.018 INFO  FeatureManager - Using codec VCFCodec to read file file:///home/gvandeweyer/elprep_streaming/VariantCalling_Test/scattered/../wesid-226998-m.haplotypecaller.final.vcf.gz

22:06:40.091 INFO  FeatureManager - Using codec IntervalListCodec to read file file:///home/gvandeweyer/elprep_streaming/VariantCalling_Test/scattered/0005-scattered.interval_list

22:06:40.375 INFO  IntervalArgumentCollection - Processing 3884963 bp from intervals

22:06:40.411 INFO  HaplotypeCaller - Done initializing engine

22:06:40.411 WARN  HaplotypeCaller - *************************************************************************

22:06:40.411 WARN  HaplotypeCaller - * DRAGEN-GATK mode enabled                                              *

22:06:40.412 WARN  HaplotypeCaller - * The following arguments have had their inputs overwritten:            *

22:06:40.412 WARN  HaplotypeCaller - * --apply-frd                                                           *

22:06:40.412 WARN  HaplotypeCaller - * --apply-bqd                                                           *

22:06:40.412 WARN  HaplotypeCaller - * --transform-dragen-mapping-quality                                    *

22:06:40.412 WARN  HaplotypeCaller - * --soft-clip-low-quality-ends                                          *

22:06:40.413 WARN  HaplotypeCaller - * --mapping-quality-threshold-for-genotyping  1                         *

22:06:40.413 WARN  HaplotypeCaller - * --minimum-mapping-quality  1                                          *

22:06:40.413 WARN  HaplotypeCaller - * --allele-informative-reads-overlap-margin  1                          *

22:06:40.413 WARN  HaplotypeCaller - * --disable-cap-base-qualities-to-map-quality                           *

22:06:40.413 WARN  HaplotypeCaller - * --enable-dynamic-read-disqualification-for-genotyping                 *

22:06:40.413 WARN  HaplotypeCaller - * --expected-mismatch-rate-for-read-disqualification  0.03              *

22:06:40.413 WARN  HaplotypeCaller - * --genotype-assignment-method USE_POSTERIOR_PROBABILITIES              *

22:06:40.414 WARN  HaplotypeCaller - * --padding-around-indels  150                                          *

22:06:40.414 WARN  HaplotypeCaller - * --standard-min-confidence-threshold-for-calling 3.0                   *

22:06:40.414 WARN  HaplotypeCaller - * --use-posteriors-to-calculate-qual                                    *

22:06:40.414 WARN  HaplotypeCaller - * --allele-informative-reads-overlap-margin  1                          *

22:06:40.414 WARN  HaplotypeCaller - *                                                                       *

22:06:40.414 WARN  HaplotypeCaller - * If you would like to run DRAGEN-GATK with different inputs for any    *

22:06:40.415 WARN  HaplotypeCaller - * of the above arguments please manually construct the command.         *

22:06:40.415 WARN  HaplotypeCaller - *************************************************************************

22:06:40.437 INFO  HaplotypeCallerEngine - Disabling physical phasing, which is supported only for reference-model confidence output

22:06:40.484 INFO  NativeLibraryLoader - Loading libgkl_utils.so from jar:file:/home/gvandeweyer/miniconda3/envs/ELPREP/share/gatk4-4.2.5.0-0/gatk-package-4.2.5.0-local.jar!/com/intel/gkl/native/libgkl_utils.so

22:06:40.485 INFO  NativeLibraryLoader - Loading libgkl_pairhmm_omp.so from jar:file:/home/gvandeweyer/miniconda3/envs/ELPREP/share/gatk4-4.2.5.0-0/gatk-package-4.2.5.0-local.jar!/com/intel/gkl/native/libgkl_pairhmm_omp.so

22:06:40.515 INFO  IntelPairHmm - Flush-to-zero (FTZ) is enabled when running PairHMM

22:06:40.516 INFO  IntelPairHmm - Available threads: 4

22:06:40.516 INFO  IntelPairHmm - Requested threads: 4

22:06:40.517 INFO  PairHMM - Using the OpenMP multi-threaded AVX-accelerated native PairHMM implementation

22:06:40.545 INFO  ProgressMeter - Starting traversal

22:06:40.545 INFO  ProgressMeter -        Current Locus  Elapsed Minutes     Regions Processed   Regions/Minute

22:06:41.344 WARN  InbreedingCoeff - InbreedingCoeff will not be calculated at position chr4:57843320 and possibly subsequent; at least 10 samples must have called genotypes

22:06:50.557 INFO  ProgressMeter -        chr4:69816964              0.2                   570           3415.9

22:07:00.633 INFO  ProgressMeter -        chr4:74352584              0.3                  1340           4002.4

22:07:10.827 INFO  ProgressMeter -        chr4:79856475              0.5                  2370           4695.9

22:07:20.846 INFO  ProgressMeter -        chr4:88243684              0.7                  3370           5017.2

22:07:32.170 INFO  ProgressMeter -        chr4:88577717              0.9                  3470           4032.9

22:07:42.172 INFO  ProgressMeter -       chr4:102816662              1.0                  4680           4556.4

22:07:52.185 INFO  ProgressMeter -       chr4:111397771              1.2                  5780           4840.9

22:08:02.254 INFO  ProgressMeter -       chr4:122599470              1.4                  6650           4883.2

22:08:12.357 INFO  ProgressMeter -       chr4:138450656              1.5                  7590           4960.1

22:08:22.425 INFO  ProgressMeter -       chr4:147561485              1.7                  8520           5017.7

22:08:32.475 INFO  ProgressMeter -       chr4:155719877              1.9                  9500           5092.5

22:08:42.564 INFO  ProgressMeter -       chr4:169393558              2.0                 10500           5163.1

22:08:52.656 INFO  ProgressMeter -       chr4:184628140              2.2                 11430           5191.1

22:09:17.262 INFO  ProgressMeter -       chr4:190878453              2.6                 12190           4667.0

22:09:31.627 INFO  ProgressMeter -          chr5:679327              2.9                 12500           4383.9

22:09:41.640 INFO  ProgressMeter -         chr5:5303312              3.0                 13080           4333.6

22:09:51.755 INFO  ProgressMeter -        chr5:15936459              3.2                 14060           4411.9

22:10:01.826 INFO  ProgressMeter -        chr5:32403384              3.4                 14710           4384.9

22:10:11.906 INFO  ProgressMeter -        chr5:38528906              3.5                 15860           4502.2

22:10:22.512 INFO  ProgressMeter -        chr5:53815458              3.7                 16970           4587.2

22:10:32.552 INFO  ProgressMeter -        chr5:64023887              3.9                 17960           4644.7

22:10:42.616 INFO  ProgressMeter -        chr5:70888653              4.0                 18930           4692.0

22:10:52.692 INFO  ProgressMeter -        chr5:78319994              4.2                 20130           4790.1

22:11:02.777 INFO  ProgressMeter -        chr5:89939520              4.4                 21130           4834.7

22:11:12.950 INFO  ProgressMeter -        chr5:96339058              4.5                 21980           4841.3

22:11:23.401 INFO  ProgressMeter -       chr5:115188609              4.7                 23170           4914.9

22:11:33.498 INFO  ProgressMeter -       chr5:127089898              4.9                 24050           4925.7

22:11:33.815 INFO  HaplotypeCaller - 69572 read(s) filtered by: MappingQualityReadFilter  

0 read(s) filtered by: MappingQualityAvailableReadFilter  

0 read(s) filtered by: MappedReadFilter  

380 read(s) filtered by: NotSecondaryAlignmentReadFilter  

0 read(s) filtered by: NotDuplicateReadFilter  

0 read(s) filtered by: PassesVendorQualityCheckReadFilter  

0 read(s) filtered by: NonZeroReferenceLengthAlignmentReadFilter  

0 read(s) filtered by: GoodCigarReadFilter  

0 read(s) filtered by: WellformedReadFilter  

69952 total reads filtered

22:11:33.816 INFO  ProgressMeter -       chr5:127488298              4.9                 24105           4931.6

22:11:33.816 INFO  ProgressMeter - Traversal complete. Processed 24105 total regions in 4.9 minutes.

22:11:33.891 INFO  VectorLoglessPairHMM - Time spent in setup for JNI call : 2.883281574

22:11:33.891 INFO  PairHMM - Total compute time in PairHMM computeLogLikelihoods() : 66.287158269

22:11:33.891 INFO  SmithWatermanAligner - Total compute time in java Smith-Waterman : 81.56 sec

22:11:35.558 INFO  HaplotypeCaller - Shutting down engine

[March 12, 2022 10:11:35 PM CET] org.broadinstitute.hellbender.tools.walkers.haplotypecaller.HaplotypeCaller done. Elapsed time: 4.94 minutes.

Runtime.totalMemory()=1998061568

===========

See forum topic details at forum guidelines page: https://gatk.broadinstitute.org/hc/en-us/articles/360053845952-Forum-Guidelines

(created from Zendesk ticket #276551)
gz#276551

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