TABIX module not working

[kainamill]

Describe the issue

Hello, I am currently using ensebl-vep/113 on an HPC system to annotate somatic variants; however, when attempting to use the --custom flag to annotate with the latest version of clinvar I am coming across this error:

MSG: ERROR: Cannot use format vcf without Bio::DB::HTS::Tabix module installed

STACK Bio::EnsEMBL::VEP::AnnotationSource::File::new /gpfs/data/icelake-apps/software/gcc-12.1.0/ensembl-vep/113/modules/Bio/EnsEMBL/VEP/AnnotationSource/File.pm:178
STACK Bio::EnsEMBL::VEP::AnnotationSourceAdaptor::get_all_custom /gpfs/data/icelake-apps/software/gcc-12.1.0/ensembl-vep/113/modules/Bio/EnsEMBL/VEP/AnnotationSourceAdaptor.pm:328
STACK Bio::EnsEMBL::VEP::AnnotationSourceAdaptor::get_all /gpfs/data/icelake-apps/software/gcc-12.1.0/ensembl-vep/113/modules/Bio/EnsEMBL/VEP/AnnotationSourceAdaptor.pm:94
STACK Bio::EnsEMBL::VEP::BaseRunner::get_all_AnnotationSources /gpfs/data/icelake-apps/software/gcc-12.1.0/ensembl-vep/113/modules/Bio/EnsEMBL/VEP/BaseRunner.pm:170
STACK Bio::EnsEMBL::VEP::Runner::init /gpfs/data/icelake-apps/software/gcc-12.1.0/ensembl-vep/113/modules/Bio/EnsEMBL/VEP/Runner.pm:128
STACK Bio::EnsEMBL::VEP::Runner::run /gpfs/data/icelake-apps/software/gcc-12.1.0/ensembl-vep/113/modules/Bio/EnsEMBL/VEP/Runner.pm:200
STACK toplevel /apps/software/gcc-12.1.0/ensembl-vep/113/vep:46
Date (localtime)    = Thu May 15 09:06:34 2025
Ensembl API version = 113
---------------------------------------------------

System

• VEP version:113

• VEP Cache version: 113

• Perl version: 5.36.0

• tabix installed under: /apps/software/gcc-12.1.0/ensembl-vep/113/htslib/tabix

Full VEP command line

vep -i $sample \
        --force_overwrite \
        --fork 7 \
        --format vcf \
        --hgvs \
        --fasta $fasta \
        --assembly GRCh37 \
        --species homo_sapiens \
        --symbol \
        --cache \
        --cache_version 113 \
        --dir_cache $cache \
        --offline \
        --show_ref_allele \
        --transcript_version \
        --gene_version \
        --af_gnomade \
        --custom file=$clinvar,short_name=ClinVar,format=vcf,type=exact,coords=1,fields=CLNSIG%CLNREVSTAT%CLNDN \
        --no_intergenic \
        --vcf \
        -o ${sample%.vcf.gz}"_anno_CLIN25.vcf.gz"

Data files (if applicable)

They include:

• clinvar file: clinvar_20250504.vcf.gz
  (clinvar file has .tbi index in same directory)

[olaaustine]

Hi @kainamill,
Hope you are well and this meets you well?
Thank you for your query.
Yes, VEP comes with its own tabix installed and this can cause a conflict which is most likely causing this error as you already have Tabix installed separately.
I suggest that you get a clean checkout of ensembl-vep and install it with the option --NO_HTSLIB
Please let us know if you have any more query or if this does not solve the problem.
Thank you.
Ola.

[kainamill]

Hi Ola, thank you for the quick response! I will let my HPC team know and let you know of any other issues/successes. Thanks!

[kainamill]

Hi Ola, unfortunately, after re-installing ensembl-vep with the --NO_HTSLIB flag, we are still coming across the same error message. Any insight as to where we can go from here?

[olaaustine]

Hi @kainamill,
Apologies for the delayed response.
Is this an issue you are still experiencing?
If so can you run this perl -e "use Bio::DB::HTS::Tabix" and let me know what the output is ?
Thank you for your patience
Ola

[kainamill]

Hi, We are still having the same issue unfortunately, and our IT department is not sure what the issue could be. Everything has been installed correctly on our end, it seems. I tried typing the command you mentioned into the command line after loading the appropriate modules and there is no output generated. Appreciate any guidance you can provide. Kaina From: Ola Austine ***@***.***> Date: Wednesday, June 18, 2025 at 10:19 AM To: Ensembl/ensembl-vep ***@***.***> Cc: Millan, Kaina [BSD] ***@***.***>, Mention ***@***.***> Subject: [EXTERNAL] Re: [Ensembl/ensembl-vep] TABIX module not working (Issue #1874) olaaustine left a comment (Ensembl/ensembl-vep#1874) Hi @kainamill, Apologies for the delayed response. Is this an issue you are still experiencing? If so can you run this perl -e "use Bio: : DB: : HTS: : Tabix" and let me know what the output is ZjQcmQRYFpfptBannerStart External: Use caution with links, attachments, and providing information. <https://us-phishalarm-ewt.proofpoint.com/EWT/v1/MyIu0v6UfBA57LoN!7t_N6e8MRR37t-qtlp-Y0YOBVTqDdLBV2NODxwOz_nI4cOhAL3gwm791xIjt69QpWzss1-AkXSozxgXyP6n3dH7wv-2n3PpzFDWHaSbaymZhNTQtNVmf$> Report Suspicious <https://us-phishalarm-ewt.proofpoint.com/EWT/v1/MyIu0v6UfBA57LoN!7t_N6e8MRR37t-qtlp-Y0YOBVTqDdLBV2NODxwOz_nI4cOhAL3gwm791xIjt69QpWzss1-AkXSozxgXyP6n3dH7wv-2n3PpzFDWHaSbaymZhNTQtNVmf$> ZjQcmQRYFpfptBannerEnd [https://avatars.githubusercontent.com/u/83219714?s=20&v=4]olaaustine left a comment (Ensembl/ensembl-vep#1874)<https://urldefense.com/v3/__https:/github.com/Ensembl/ensembl-vep/issues/1874*issuecomment-2984659396__;Iw!!MyIu0v6UfBA57LoN!68bZIBIvMa-shnDp8zmqhPQkk3Eq3uHdtl1l9EaMoLc-eGfwzqglxZBSiEkixOIJrpQqdVeorYf2w6NXoRzyX4qjZAWnIm2UHw$> Hi @kainamill<https://urldefense.com/v3/__https:/github.com/kainamill__;!!MyIu0v6UfBA57LoN!68bZIBIvMa-shnDp8zmqhPQkk3Eq3uHdtl1l9EaMoLc-eGfwzqglxZBSiEkixOIJrpQqdVeorYf2w6NXoRzyX4qjZAVjcJmQow$>, Apologies for the delayed response. Is this an issue you are still experiencing? If so can you run this perl -e "use Bio::DB::HTS::Tabix" and let me know what the output is ? Thank you for your patience Ola — Reply to this email directly, view it on GitHub<https://urldefense.com/v3/__https:/github.com/Ensembl/ensembl-vep/issues/1874*issuecomment-2984659396__;Iw!!MyIu0v6UfBA57LoN!68bZIBIvMa-shnDp8zmqhPQkk3Eq3uHdtl1l9EaMoLc-eGfwzqglxZBSiEkixOIJrpQqdVeorYf2w6NXoRzyX4qjZAWnIm2UHw$>, or unsubscribe<https://urldefense.com/v3/__https:/github.com/notifications/unsubscribe-auth/BM3EUWRS5XZUO2T6YLW7U4T3EF7PBAVCNFSM6AAAAAB5GQC5BWVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDSOBUGY2TSMZZGY__;!!MyIu0v6UfBA57LoN!68bZIBIvMa-shnDp8zmqhPQkk3Eq3uHdtl1l9EaMoLc-eGfwzqglxZBSiEkixOIJrpQqdVeorYf2w6NXoRzyX4qjZAXdxLcWrA$>. You are receiving this because you were mentioned.Message ID: ***@***.***>

…

________________________________ This message was received from outside of the organization. Please pay special attention and practice care when clicking on any links or providing any information to the sender. Cyber attacks commonly attempt to trick you in to thinking the sender is a reputable individual who you can trust.

________________________________

[sgiorgetti]

Hello Variation - @olaaustine @dglemos it looks like another user has similar issue also with 113.
They posted into the Bio::DB::HTS repo; please, find link below.

Ensembl/Bio-DB-HTS#111

Thanks

[olaaustine]

Hi @kainamill,
From the stack trace posted here 111, it seems Bio::DB::HTS::Tabix is not installed properly or the module is not in PERL5LIB (or seen by Perl anyway).
Can you run the command which tabix and let us know the output.
Thank you