Funcotator logic bug #6289

tmm211 · 2019-11-27T21:54:11Z

Bug Report

Affected tool(s) or class(es)

Funcotator

Affected version(s)

v.4.1.3.0 using us.gcr.io/broad-gatk/gatk:4.1.3.0
11/22 failed in Terra

Description

There is a bug in the logic with how Funcotator is handling this variant. It is a variant after
chr14:24655355
Stacktrace

Jonn has the input files, log file, and WDL.

Steps to reproduce

To reproduce this issue, all the inputs and full pipeline are listed in this Zendesk ticket 3847. Contact Tiffany for access

Expected behavior

The tool should handle this situation more gracefully?

Actual behavior

It fails with a java.lang.StringIndexOutOfBoundsException: String index out of range: 776

lincoln-harris · 2020-01-13T19:35:47Z

hey guys I'm seeing the same error

jonn-smith · 2020-01-21T21:12:47Z

@tmm211 @lincoln-harris I'll put this back on my radar. Thanks for your patience.

lydiarck · 2020-01-22T19:52:34Z

I have the same error; let me know if it would be helpful to have my input files, logs, etc. I'm seeing it in version 4.1.4.0.

shandy79 · 2020-02-06T18:20:36Z

Also seeing this in 4.1.4.1. From my testing, this is happening back through version 4.1.1.0, with 4.1.0.0 being unaffected.

tmm211 · 2020-07-13T16:47:32Z

@jonn-smith I am working with someone on a featured workspace for a paper that will likely highlight this issue. Any thoughts on when it will get prioritized?

jonn-smith · 2020-07-13T16:49:39Z

I'm going to review all the Funcotator issues in the next few weeks and start addressing them then.

jonn-smith · 2020-07-13T18:12:42Z

The example variant from the above Terra run is:

chr14   24655355        .       C       CG      .       .

DadongZ · 2020-09-08T16:00:03Z

I got same error for gatk 4.1.8.0. Any solutions?

jonn-smith · 2020-09-08T16:34:18Z

This will be the next bug I look into. It's part of a family of issues that all relate to how the predicted protein change is created.

samanthahv · 2020-11-25T16:03:39Z

Another user reported having the same issue with gatk 4.1.7.0

alanhoyle · 2021-02-22T16:46:11Z

I am seeing this same error with gatk 4.1.9.0. At the very least, it would be nice if Funcotator caught the error and printed a warning, omitted the problematic variant, and continued instead of crashing and leaving truncated output. the VCF I'm annotating is WGS with 150+ samples, and it's crashing on a variant on chr9.

jonn-smith · 2021-02-22T17:00:09Z

@alanhoyle This is on the todo list for this quarter - there are a variety of similar issues with the protein change string that should all be resolved together.

alanhoyle · 2021-02-22T20:05:00Z

Thank you. The line(s) that are causing the problem for me begin as follows:

chr9    67726241        .       T       A     104    PASS
chr9    67726241        .       TCA     TCACACA,TCACACACA,TCACA,T    182	PASS

This seems to be an interesting position.

jonn-smith · 2021-02-22T20:06:21Z

Thanks for the test case! From what I've seen in the past this issue happens with indels, so this makes sense to me.

alanhoyle · 2021-02-22T23:14:26Z

After a good deal of editing, this is an almost minimal complete VCF that throws the error (GRCh38):

##fileformat=VCFv4.1
##contig=<ID=chr9,length=138394717>
##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO	FORMAT	Sample
chr9	67726241	.	TCA	TCACACA,TCACACACA	182	PASS	.	GT	./.

The actual error I'm getting is this:

[February 22, 2021 11:11:51 PM UTC] org.broadinstitute.hellbender.tools.funcotator.Funcotator done. Elapsed time: 0.12 minutes.
Runtime.totalMemory()=2552233984
java.lang.StringIndexOutOfBoundsException: String index out of range: 117
	at java.lang.String.substring(String.java:1963)
	at org.broadinstitute.hellbender.tools.funcotator.ProteinChangeInfo.initializeForInsertion(ProteinChangeInfo.java:256)
	at org.broadinstitute.hellbender.tools.funcotator.ProteinChangeInfo.<init>(ProteinChangeInfo.java:93)
	at org.broadinstitute.hellbender.tools.funcotator.ProteinChangeInfo.create(ProteinChangeInfo.java:371)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createSequenceComparison(GencodeFuncotationFactory.java:2045)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createCodingRegionFuncotationForProteinCodingFeature(GencodeFuncotationFactory.java:1235)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createExonFuncotation(GencodeFuncotationFactory.java:1086)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createGencodeFuncotationOnSingleTranscript(GencodeFuncotationFactory.java:1020)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createFuncotationsHelper(GencodeFuncotationFactory.java:847)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createFuncotationsHelper(GencodeFuncotationFactory.java:831)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.lambda$createGencodeFuncotationsByAllTranscripts$0(GencodeFuncotationFactory.java:508)
	at java.util.stream.ReferencePipeline$3$1.accept(ReferencePipeline.java:193)
	at java.util.ArrayList$ArrayListSpliterator.forEachRemaining(ArrayList.java:1384)
	at java.util.stream.AbstractPipeline.copyInto(AbstractPipeline.java:482)
	at java.util.stream.AbstractPipeline.wrapAndCopyInto(AbstractPipeline.java:472)
	at java.util.stream.ReduceOps$ReduceOp.evaluateSequential(ReduceOps.java:708)
	at java.util.stream.AbstractPipeline.evaluate(AbstractPipeline.java:234)
	at java.util.stream.ReferencePipeline.collect(ReferencePipeline.java:566)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createGencodeFuncotationsByAllTranscripts(GencodeFuncotationFactory.java:509)
	at org.broadinstitute.hellbender.tools.funcotator.dataSources.gencode.GencodeFuncotationFactory.createFuncotationsOnVariant(GencodeFuncotationFactory.java:564)
	at org.broadinstitute.hellbender.tools.funcotator.DataSourceFuncotationFactory.determineFuncotations(DataSourceFuncotationFactory.java:243)
	at org.broadinstitute.hellbender.tools.funcotator.DataSourceFuncotationFactory.createFuncotations(DataSourceFuncotationFactory.java:211)
	at org.broadinstitute.hellbender.tools.funcotator.DataSourceFuncotationFactory.createFuncotations(DataSourceFuncotationFactory.java:182)
	at org.broadinstitute.hellbender.tools.funcotator.FuncotatorEngine.lambda$createFuncotationMapForVariant$0(FuncotatorEngine.java:147)
	at java.util.stream.ReferencePipeline$3$1.accept(ReferencePipeline.java:193)
	at java.util.stream.ReferencePipeline$2$1.accept(ReferencePipeline.java:175)
	at java.util.ArrayList$ArrayListSpliterator.forEachRemaining(ArrayList.java:1384)
	at java.util.stream.AbstractPipeline.copyInto(AbstractPipeline.java:482)
	at java.util.stream.AbstractPipeline.wrapAndCopyInto(AbstractPipeline.java:472)
	at java.util.stream.ReduceOps$ReduceOp.evaluateSequential(ReduceOps.java:708)
	at java.util.stream.AbstractPipeline.evaluate(AbstractPipeline.java:234)
	at java.util.stream.ReferencePipeline.collect(ReferencePipeline.java:566)
	at org.broadinstitute.hellbender.tools.funcotator.FuncotatorEngine.createFuncotationMapForVariant(FuncotatorEngine.java:157)
	at org.broadinstitute.hellbender.tools.funcotator.Funcotator.enqueueAndHandleVariant(Funcotator.java:907)
	at org.broadinstitute.hellbender.tools.funcotator.Funcotator.apply(Funcotator.java:861)
	at org.broadinstitute.hellbender.engine.VariantWalker.lambda$traverse$0(VariantWalker.java:104)
	at java.util.stream.ForEachOps$ForEachOp$OfRef.accept(ForEachOps.java:183)
	at java.util.stream.ReferencePipeline$3$1.accept(ReferencePipeline.java:193)
	at java.util.stream.ReferencePipeline$2$1.accept(ReferencePipeline.java:175)
	at java.util.stream.ReferencePipeline$3$1.accept(ReferencePipeline.java:193)
	at java.util.Iterator.forEachRemaining(Iterator.java:116)
	at java.util.Spliterators$IteratorSpliterator.forEachRemaining(Spliterators.java:1801)
	at java.util.stream.AbstractPipeline.copyInto(AbstractPipeline.java:482)
	at java.util.stream.AbstractPipeline.wrapAndCopyInto(AbstractPipeline.java:472)
	at java.util.stream.ForEachOps$ForEachOp.evaluateSequential(ForEachOps.java:150)
	at java.util.stream.ForEachOps$ForEachOp$OfRef.evaluateSequential(ForEachOps.java:173)
	at java.util.stream.AbstractPipeline.evaluate(AbstractPipeline.java:234)
	at java.util.stream.ReferencePipeline.forEach(ReferencePipeline.java:485)
	at org.broadinstitute.hellbender.engine.VariantWalker.traverse(VariantWalker.java:102)
	at org.broadinstitute.hellbender.engine.GATKTool.doWork(GATKTool.java:1049)
	at org.broadinstitute.hellbender.cmdline.CommandLineProgram.runTool(CommandLineProgram.java:140)
	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)

lydiarck · 2021-08-31T13:07:18Z

Is there an update on this? Thanks!

jnktsj · 2021-09-04T18:01:22Z

While searching the error, I found this github issue! I'm having the same error with gatk 4.2.0.0… GP is trying to incorporate Funcotator into the clinical pipeline, it would be great if this fix can be made as soon as possible. Thanks!
cc: @NiallJLennon @CarrieCibulskis

jonn-smith · 2021-09-04T22:16:18Z

@lydiarck - Not yet our priorities shifted and I haven't had time to address this.

@jnktsj That's great to hear! I'm surprised because this is the first I've heard of it. If you have some time, I'd love to discuss it with you (and / or Niall and / or Carrie). I'm particularly interested in how you will incorporate new versions of the software as updates are made.

Things are starting to slow down, so I should actually be able to start taking a look next or the following week. It's going to require refactoring several things deep in the Funcotator Engine, which is why it hasn't happened yet.

jkobject · 2021-10-14T19:37:15Z

Hi, getting the same error trying to run this new mutect2 pipeline on CCLE. We will not annotate mutect2 with funcotator in the meantime but would also be very useful to us if this problem is solved! (it impacts ~15% of our samples)

Thank you @jonn-smith !

droazen · 2021-10-14T20:08:51Z

@jkobject @jnktsj Thanks for the reports -- we are going to prioritize a fix for this issue this quarter!

droazen · 2021-10-21T16:42:06Z

@jkobject @jnktsj @lydiarck We have a prospective fix for this issue that at least avoids the crash: #7513

It should be part of the next GATK release, or you can try it out yourself if you're comfortable building the GATK from source.

jonn-smith · 2021-10-25T19:57:14Z

OK, guys. I just merged in a fix for this. If you have a chance, give it another try with the latest GATK main branch.

@jnktsj @alanhoyle @jkobject @DadongZ @lincoln-harris @lydiarck @shandy79 @samanthahv

alanhoyle · 2021-10-25T19:59:55Z

@jonn-smith is this in a release or would we have to download/compile to test?

jonn-smith · 2021-10-25T20:09:12Z

@alanhoyle Right now it's just in the code, so you'd have to compile it. If you can wait, we're planning on doing a release sometime in the next week or two.

jkobject · 2022-06-29T01:19:34Z

Hello, Having run it now on all our samples we still see this error.

It only happens on the WES (1800 samples) only in 13 of them. It does not happen for the WGS (600samples).

This is in GATK 4.2.6.1.

Let me know if you want us to share some example in a workspace.

grimmem1 · 2024-02-27T21:55:45Z

Has this bug been addressed in recent Funcotator versions? If so, which version?

jonn-smith added the Funcotator label Jan 21, 2020

droazen added the bug label Sep 8, 2020

droazen assigned jonn-smith Sep 8, 2020

jonn-smith mentioned this issue Oct 25, 2021

Add integration tests in Funcotator for out of bounds variants #7523

Open

jonn-smith closed this as completed Oct 25, 2021

gbrandt6 mentioned this issue Nov 9, 2021

Funcotator Exception: String index out of range #6651

Open

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Funcotator logic bug #6289

Funcotator logic bug #6289

tmm211 commented Nov 27, 2019

lincoln-harris commented Jan 13, 2020

jonn-smith commented Jan 21, 2020

lydiarck commented Jan 22, 2020

shandy79 commented Feb 6, 2020 •

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tmm211 commented Jul 13, 2020

jonn-smith commented Jul 13, 2020

jonn-smith commented Jul 13, 2020

DadongZ commented Sep 8, 2020

jonn-smith commented Sep 8, 2020

samanthahv commented Nov 25, 2020

alanhoyle commented Feb 22, 2021

jonn-smith commented Feb 22, 2021

alanhoyle commented Feb 22, 2021

jonn-smith commented Feb 22, 2021

alanhoyle commented Feb 22, 2021

lydiarck commented Aug 31, 2021

jnktsj commented Sep 4, 2021

jonn-smith commented Sep 4, 2021 •

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jkobject commented Oct 14, 2021

droazen commented Oct 14, 2021

droazen commented Oct 21, 2021

jonn-smith commented Oct 25, 2021

alanhoyle commented Oct 25, 2021

jonn-smith commented Oct 25, 2021

jkobject commented Jun 29, 2022

grimmem1 commented Feb 27, 2024

Funcotator logic bug #6289

Funcotator logic bug #6289

Comments

tmm211 commented Nov 27, 2019

Bug Report

Affected tool(s) or class(es)

Affected version(s)

Description

Steps to reproduce

Expected behavior

Actual behavior

lincoln-harris commented Jan 13, 2020

jonn-smith commented Jan 21, 2020

lydiarck commented Jan 22, 2020

shandy79 commented Feb 6, 2020 • edited Loading

tmm211 commented Jul 13, 2020

jonn-smith commented Jul 13, 2020

jonn-smith commented Jul 13, 2020

DadongZ commented Sep 8, 2020

jonn-smith commented Sep 8, 2020

samanthahv commented Nov 25, 2020

alanhoyle commented Feb 22, 2021

jonn-smith commented Feb 22, 2021

alanhoyle commented Feb 22, 2021

jonn-smith commented Feb 22, 2021

alanhoyle commented Feb 22, 2021

lydiarck commented Aug 31, 2021

jnktsj commented Sep 4, 2021

jonn-smith commented Sep 4, 2021 • edited Loading

jkobject commented Oct 14, 2021

droazen commented Oct 14, 2021

droazen commented Oct 21, 2021

jonn-smith commented Oct 25, 2021

alanhoyle commented Oct 25, 2021

jonn-smith commented Oct 25, 2021

jkobject commented Jun 29, 2022

grimmem1 commented Feb 27, 2024

shandy79 commented Feb 6, 2020 •

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jonn-smith commented Sep 4, 2021 •

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