faster variant annotation for large VCFs

Question

[Amitm]

hi there,

I am trying to annotate WGS VCF files through VEP, and even on multi-threading (n=8) the process is painfully slow. The VCF sizes range between 1-1.5Gb. Around 2 days for each VCF

What would you recommend to speed up the process? I can break the VCF into chunks. Any other sol. or software reco.? Apart from gene & functional impact level anno., I am using VEP plugins for CADD and gnomAD genome based freq.

Thanks

[ATpoint]

There is a parameter --buffer-size that controls how many variants are loaded into memory. Double-check with the manual, as this might substantially increase speed if you have the RAM available.

[Amitm]

many thanks! Going to try this

[Amitm]

Thanks again. With 2x the buffer size than default and n=16 threads the process completed in ~7hrs!

[Chan]

Hi,

I see that you have used CADD plugin fro VEP. Could you please let me know how you did it. It does not work for me and gives me a blank column of CADD scores.

Thank You

[ATpoint]

'does not work' is not a helpful error message. How did you install and run it?

[Chan]

I am trying to run by using "--plugin CADD, path/to/ InDels_inclAnno.tsv.gz,path/to/ whole_genome_SNVs_inclAnno.tsv.gz".But the column with CADD is blank in the output.

Thanks

[Amitm]

Hi, Have you been able to make it work? After installing VEP, you need to have run -

perl \
INSTALL.pl \
--AUTO p \
--PLUGINS CADD,ExAC \
--SPECIES homo_sapiens_merged \
--ASSEMBLY GRCh37

That would configure the plugins (you specify) under the vep data cache Plugins/ path. You would get msg like this -

 - installing "CADD"
 - This plugin requires data
 - See /Users/akmandal/.vep/Plugins/CADD.pm for details
 - OK

Once done, I created a dir. -> .vep/Plugins/dat_CADD_1.3 and downloaded whole_genome_SNVs.tsv.gz & InDels.tsv.gz (along with their index files). Then providing this arg. to VEP run -

--plugin CADD,/path/to/dat_CADD_1.3/whole_genome_SNVs.tsv.gz,/path/to/dat_CADD_1.3/InDels.tsv.gz \

does the job.

Answer 1

[Emily]

There's some information about VEP speed in this blog post. Your plugins are probably slowing you down a bit as they have to communicate with databases rather than using your offline cache, which can be slower – I'm afraid there's not a lot you can do about that.