[ensembl-dev] VEP "Fork of Death" possible interaction between --hgvs/--check_ref

Will McLaren wm2 at ebi.ac.uk
Thu Jun 27 16:24:43 BST 2013


Hello Stuart,

Thanks for finding the problem here. I've patched in a fix on CVS, so you
should pick it up if you update your ensembl-variation API checkout or
re-run INSTALL.pl

The issue was that warnings from --check_ref (and from HGVS if there was an
issue with alleles/strands) were causing forked processes to die rather
than just warn and continue.

Regards

Will McLaren
Ensembl Variation


On 27 June 2013 15:39, Stuart Watt <Stuart.Watt at oicr.on.ca> wrote:

>  Hi all
>
>  I found an interesting corner case for another VEP "fork of death"
> problem. I managed to replicate it fairly successfully, but haven't had a
> chance to pin it down.
>
>  The scenario is: I'm using a subset of COSMIC in a fairly large (700k
> variants) input file. I'm using both --hgvs and --check_ref, and they seem
> to interact. Using --hgvs alone works. Using both in non-fork mode I get
> sometimes got errors about reference alleles and variant alleles being the
> same. In fork mode the same parameters throw an error, possibly as the
> errors leak into data communications. What is odd is that these errors went
> away when --check_ref was not used, and that when I checked the lines
> reporting errors, the alleles were in fact different. It is as if something
> accessed or revealed by --check_ref is being modified behind the scenes,
> triggering the HGVS errors.
>
>    - Succeeds: perl -X
>    /Users/swatt/ensembl/ensembl-tools/scripts/variant_effect_predictor/
>    variant_effect_predictor.pl --format ensembl --offline --no_progress
>    --canonical --check_existing --force_overwrite --numbers --buffer_size 5000
>    --sift b --polyphen b --compress gzcat --fasta /Users/swatt/fasta
>    --input_file vep1.txt --output_file vep1.vep_output --hgvs --fork 8
>    - Fails (Fork of Death): perl -X
>    /Users/swatt/ensembl/ensembl-tools/scripts/variant_effect_predictor/
>    variant_effect_predictor.pl --format ensembl --offline --no_progress
>    --canonical --check_existing --force_overwrite --numbers --buffer_size 5000
>    --sift b --polyphen b --compress gzcat --fasta /Users/swatt/fasta
>    --input_file vep1.txt --output_file vep1.vep_output --hgvs --fork 8
>    --check_ref
>    - Succeeds (probably, eventually, but it takes a very long time): perl
>    -X /Users/swatt/ensembl/ensembl-tools/scripts/variant_effect_predictor/
>    variant_effect_predictor.pl --format ensembl --offline --no_progress
>    --canonical --check_existing --force_overwrite --numbers --buffer_size 5000
>    --sift b --polyphen b --compress gzcat --fasta /Users/swatt/fasta
>    --input_file vep1.txt --output_file vep1.vep_output --hgvs --check_ref
>
> The only options that seem to determine these behaviours are --fork,
> --check_ref, and --hgvs, but I haven't exhaustively factored out the other
> options.
>
>  Despite this, I can now complete the full file in fork mode on OSX, and
> that saves me many hours. So thanks for all the great work on these issues
> so far.
>
>  I'm happy to provide data files and other info if required. If anybody
> has any tips in debugging this, I may get time to peek further into the
> perl code and figure out where things go funny.
>
>  Configuration info:
> OSX - Lion
>  perl - 5.16.1 (not system perl, built using perlbrew)
>  Ensembl/VEP version 72
>
> All the best
> Stuart
>
> --
>  *Stuart Watt, PhD*
>
> Scientific Associate
>
> *Ontario Institute for Cancer Research*
>
> MaRS Centre, South Tower
> 101 College Street, Suite 800
> Toronto, Ontario, Canada M5G 0A3
>
> Toll-free: 1-866-678-6427
> www.oicr.on.ca
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