MaveDB fields empty

[dade7]

MaveDB fields empty

[nuno-agostinho]

Hey @dade7,

Hope you are having a great day.

Not sure if this is related, but we merged a bug fix recently for regulatory regions in MaveDB plugin (#628). At least, it should take care of the warnings you are getting.

Can you send me some of your input variants to test your issue? Are you sure those variants are available in MaveDB annotation?

Thanks,
Nuno

[dade7]

Dear @nuno-agostinho,
here are two variants affecting PTEN and TP53. I checked it, there are scores in the MaveDB-file. However, I do not get the annotation using the Plugin.
Thanks for your help, best Dagmar

10 87957955 . C T 209 PASS
17 7674263 . A G . PASS

[nuno-agostinho]

Hey @dade7,

I can replicate your issue: the plugin is not returning any annotation for those two variants using the MaveDB plugin from release 110, returning instead many warnings:

Smartmatch is experimental at /plugins/MaveDB.pm line 120.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.
Use of uninitialized value in string eq at /plugins/MaveDB.pm line 207.
Use of uninitialized value in split at /plugins/MaveDB.pm line 207.

The good news is that we already fixed the issues you mentioned and the fix will be available in release 111.

As I understand this may not be optimal, I can give you a quick workaround to make MaveDB plugin work in the meantime: you can simply replace the file MaveDB.pm from your plugins folder (/software/vep_data_hg38/Plugins, according to your command) with the latest version of the MaveDB.pm from here: https://github.com/Ensembl/VEP_plugins/blob/main/MaveDB.pm

I am sorry for any inconvenience and hope that this workaround helps. Tell me if you need further support.

Cheers,
Nuno

[dade7]

Dear @nuno-agostinho,
thanks for your help and the workaround. I still get the following warning but I do get MaveDB info.
Best, Dagmar

WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /software/vep_data_hg38/Plugins/MaveDB.pm line 191, <$fh> line 274221.

[nuno-agostinho]

Hey @dade7,

Good to know that at least you are now getting some results.

I was not able to replicate the warning. Are you getting those warnings when using the input variants that you sent? If not, could you send some variants that show those warnings? Thanks!

Cheers,
Nuno

[abu7mead]

Hello @nuno-agostinho ,
Firstly, thanks for your help and support!
I'm also trying to run vep in offline mode and facing the same issue as the below warnings:

WARNING: 12933 : WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192, <__ANONIO__> line 7878.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192, <__ANONIO__> line 7878.
WARNING: 12937 : WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192.
WARNING: 12946 : WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192, <__ANONIO__> line 12878.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192, <__ANONIO__> line 12878.
WARNING: 13189 : WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192, <__ANONIO__> line 85963.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /home/ensembl/.vep/Plugins/MaveDB.pm line 192, <__ANONIO__> line 85963.

[nuno-agostinho]

Hey @abu7mead, sorry to hear that.

Could you check if this solution solves your issue?

you can simply replace the file MaveDB.pm from your plugins folder (/software/vep_data_hg38/Plugins, according to your command) with the latest version of the MaveDB.pm from here: main/MaveDB.pm

If not, could you please give me the input variants that you are having trouble with?

Thank you.

Best regards,
Nuno

[abu7mead]

Hi @nuno-agostinho,

Yes, I got the latest MaveDB.pm file (10,099 bytes) but same error.

this is the full command I use: -sorry for long command-

./vep -v -i /media/sf_ensembl/input/test.vcf --output_file /media/sf_ensembl/result/test_output.vcf --offline --species homo_sapiens --assembly GRCh38 --format vcf --vcf --cache --dir_cache=/media/sf_ensembl/cache/ --fork 4 --fasta /media/sf_ensembl/FASTA/Homo_sapiens.GRCh38.dna.primary_assembly.fa.gz --plugin MaveDB,file=/media/sf_ensembl/MaveDB/MaveDB_variants.tsv.gz,cols=all --pubmed --freq_pop 1KG_ALL --check_existing --af --numbers --canonical --distance 5000 --mirna --plugin NMD --plugin UTRAnnotator,file=/media/sf_ensembl/UTRAnnotator/uORF_starts_ends_GRCh38_PUBLIC.txt --mane --plugin mutfunc,db=/media/sf_ensembl/mutfunc/mutfunc_data.db --plugin IntAct,mutation_file=/media/sf_ensembl/IntAct/mutations.tsv,mapping_file=/media/sf_ensembl/IntAct/mutation_gc_map.txt.gz,feature_ac=1,feature_annotation=1,interaction_participants=1,pmid=1 --regulatory --plugin Phenotypes,phenotype_feature=1,exclude_sources=COSMIC&HGMD-PUBLIC&Cancer_Gene_Census --plugin GO,remote --plugin DisGeNET,file=/media/sf_ensembl/DisGeNET/all_variant_disease_pmid_associations_final.tsv.gz,disease=1 --plugin Mastermind,file=/media/sf_ensembl/Mastermind/mastermind_cited_variants_reference-2021.08.03-grch38.vcf.gz,mutations=1,var_iden=1,url=1 --sift b --polyphen b --plugin dbNSFP,/media/sf_share/dbNSFP/dbNSFP4.5a.txt.gz,LRT_score,LRT_pred,MutationTaster_score,MutationTaster_pred,MutationTaster_model,MutationAssessor_score,MutationAssessor_pred,FATHMM_score,FATHMM_pred,PROVEAN_score,PROVEAN_pred,MetaSVM_score,MetaSVM_pred,M-CAP_score,M-CAP_pred,MutPred_score,DEOGEN2_score,DEOGEN2_pred,ClinPred_score,ClinPred_pred,LIST-S2_score,LIST-S2_pred,CADD_phred,DANN_score,phyloP100way_vertebrate,phastCons100way_vertebrate,ExAC_AC,clinvar_id,clinvar_clnsig,clinvar_trait,clinvar_hgvs,clinvar_MedGen_id --plugin EVE,file=/media/sf_ensembl/EVE/eve_merged.vcf.gz --plugin dbscSNV,/media/sf_ensembl/dbscSNV/dbscSNV1.1_GRCh38.txt.gz --plugin MaxEntScan,/media/sf_ensembl/MaxEntScan/fordownload --plugin CADD,/media/sf_ensembl/CADD/prescored/GRCh38_v1.6/no_anno/whole_genome_SNVs.tsv.gz,/media/sf_ensembl/CADD/prescored/GRCh38_v1.6/no_anno/gnomad.genomes.r3.0.indel.tsv.gz --plugin SpliceAI,snv=/media/sf_ensembl/SpliceAI/spliceai_scores.masked.snv.hg38.vcf.gz,indel=/media/sf_ensembl/SpliceAI/spliceai_scores.masked.indel.hg38.vcf.gz --plugin Blosum62

[dade7]

test_github.zip

Dear @nuno-agostinho,
please apologize the delay. Enclosed I am sending you the file that gives the following warnings (using the new MaveDB.pm file).
Best, Dagmar

Smartmatch is experimental at /opt/vep/src/ensembl-vep/modules/Bio/EnsEMBL/VEP/AnnotationSource/File.pm line 472.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /software/vep_data_hg38/Plugins/MaveDB.pm line 191, <ANONIO> line 250946.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /software/vep_data_hg38/Plugins/MaveDB.pm line 191, <ANONIO> line 268547.
WARNING: Plugin 'MaveDB' went wrong: Can't locate object method "get_reference_TranscriptVariationAllele" via package "Bio::EnsEMBL::Variation::RegulatoryFeatureVariation" at /software/vep_data_hg38/Plugins/MaveDB.pm line 191, <ANONIO> line 274221.

[nuno-agostinho]

Hi @dade7 and @abu7mead,

This issue is related with a call to a function not available when processing RegulatoryFeatures and MotifFeatures (when --regulatory flag is enabled). I updated the code of the MaveDB plugin to skip this check in such cases. The updated fix will be officially available in VEP 111.

Again, in the meantime, you can update the MaveDB plugin file from https://github.com/Ensembl/VEP_plugins/blob/main/MaveDB.pm and those warnings should not occur anymore.

I am sorry for the inconvenience and thank you both for helping me solving this issue.

Best,
Nuno