INFO: disabling SIFT, POLYPHEN ...

[madzafv]

I'm running ~/install/ensembl-vep-release-96/vep -i cut_wbm_par5_fil_genes.vcf -o test.txt --species taeniopygia_guttata --cache --dir_cache ./ --force_overwrite --canonical --symbol --tab --everything

and getting this

2019-06-21 20:25:45 - INFO: disabling SIFT
2019-06-21 20:25:45 - INFO: disabling PolyPhen
2019-06-21 20:25:45 - INFO: Database will be accessed when using --hgvs
2019-06-21 20:25:45 - INFO: Database will be accessed when using --hgvsc
2019-06-21 20:25:45 - INFO: Database will be accessed when using --hgvsp

and the program freezes outputting

## ENSEMBL VARIANT EFFECT PREDICTOR v96.3
## Output produced at 2019-06-21 20:25:45
## Connected to taeniopygia_guttata_core_96_1 on ensembldb.ensembl.org
## Using cache in ./taeniopygia_guttata/96_taeGut3.2.4
## Using API version 96, DB version 96
## ensembl-funcgen version 96.d901739
## ensembl-variation version 96.617872b
## ensembl version 96.af6c2b8
## ensembl-io version 96.6e65b30
## genebuild version 2009-02
...

## MAX_AF_POPS : Populations in which maximum allele frequency was observed
## CLIN_SIG : ClinVar clinical significance of the dbSNP variant
## SOMATIC : Somatic status of existing variant
## PHENO : Indicates if existing variant(s) is associated with a phenotype, disease or trait; multiple values correspond to multiple variants
## PUBMED : Pubmed ID(s) of publications that cite existing variant
## MOTIF_NAME : The source and identifier of a transcription factor binding profile (TFBP) aligned at this position
## MOTIF_POS : The relative position of the variation in the aligned TFBP
## HIGH_INF_POS : A flag indicating if the variant falls in a high information position of the TFBP
## MOTIF_SCORE_CHANGE : The difference in motif score of the reference and variant sequences for the TFBP
#Uploaded_variation     Location        Allele  Gene    Feature Feature_type    Consequence     cDNA_position   CDS_position    Protein_position        Amino_acids   Codons  Existing_variation      IMPACT  DISTANCE        STRAND  FLAGS   VARIANT_CLASS   SYMBOL  SYMBOL_SOURCE   HGNC_ID BIOTYPE CANONICAL       TSL     APPRIS  CCDS  ENSP    SWISSPROT       TREMBL  UNIPARC GENE_PHENO      EXON    INTRON  DOMAINS miRNA   HGVSc   HGVSp   HGVS_OFFSET     AF      AFR_AF  AMR_AF  EAS_AF  EUR_AF  SAS_AFAA_AF   EA_AF   gnomAD_AF       gnomAD_AFR_AF   gnomAD_AMR_AF   gnomAD_ASJ_AF   gnomAD_EAS_AF   gnomAD_FIN_AF   gnomAD_NFE_AF   gnomAD_OTH_AF   gnomAD_SAS_AF   MAX_AFMAX_AF_POPS     CLIN_SIG        SOMATIC PHENO   PUBMED  MOTIF_NAME      MOTIF_POS       HIGH_INF_POS    MOTIF_SCORE_CHANGE

What could be going on?

[dglemos]

Hello @madzayasodara, Thank you for the detailed question. The messages that you get are just warnings/info: 1) you're using --everything which switches on --sift b and --polyphen b. SIFT and PolyPhen don't support your species that's why you get the message 'disabling ...' you can see here which species have SIFT results;
2) --everything also switches on --hgvs. In this case, there's two ways to get the hgvs: database or a fasta file. In your case you didn't input a fasta, and by default the database is going to be used ('Database will be accessed when using --hgvs'). About the output, it could be a problem with your input file. Could you please send your file?

[madzafv]

Got it. I don't know which one of the things I did fixed the problem... I can run vep locally now, but when I submit to the cluster's job scheduler, it complains about not finding perl modules. I try to install with cpan Try::Tiny but I get 'Do not have write permissions on '/usr/local/share/man/man3'. How can I install these modules locally and point the program to use them? I checked and I'm using the perl global installation. Should I open another issue on this? thxs!

[dglemos]

Try::Tiny is not a vep requirement anymore, here you can see the current requirements for vep installation. Could you run your vep command in the cluster and put here the error message you get?

[madzafv]

I installed perl5 and it's modules locally following instructions from this guy https://gist.github.com/ckandoth/1f01d8f3692bb8de7f2929f259a4035f
and it's working now.

When I do

~/install/ensembl-vep-release-96/vep -i cut_wbm_par5_fil_genes.vcf -o test.txt --species taeniopygia_guttata --cache --dir_cache ./ --force_overwrite --canonical --symbol --tab --everything

I get that info

2019-06-21 20:25:45 - INFO: disabling SIFT
2019-06-21 20:25:45 - INFO: disabling PolyPhen
2019-06-21 20:25:45 - INFO: Database will be accessed when using --hgvs
2019-06-21 20:25:45 - INFO: Database will be accessed when using --hgvsc
2019-06-21 20:25:45 - INFO: Database will be accessed when using --hgvsp

(which I get it now)

the program starts to runs and reads few thousands of my vcf file and then gets stuck.

This doesn't happen when I don't use --everything...

[dglemos]

How many variants does your file have? If it's a big file and you're using --everything vep is going to load a lot of data at the same time. By default --buffer_size is 5000 which means vep reads into memory 5000 variants simultaneously. Could you run with --buffer_size 500 and see if it helps? buffer size documentation

[madzafv]

Yes this worked. Thank you!