slivar is a set of command-line tools that enables rapid querying and filtering of VCF files. It facilitates operations on trios and groups and allows arbitrary expressions using simple javascript.

use cases for slivar:

• annotate variants with gnomad allele frequencies from combined exomes + whole genomes at > 30K variants/second using only a 1.5GB compressed annotation file.
• call denovo variants with a simple expression that uses mom, dad, kid labels that is applied to each trio in a cohort (as inferred from a pedigree file). kid.het && mom.hom_ref && dad.hom_ref && kid.DP > 10 && mom.DP > 10 && dad.DP > 10
• define and filter on arbitrary groups with labels. For example, 7 sets of samples each with 1 normal and 3 tumor time-points: normal.AD[0] = 0 && tumor1.AB < tumor2.AB && tumor2.AB < tumor3.AB
• filter variants with simple expressions: variant.call_rate > 0.9 && variant.FILTER == "PASS" && INFO.AC < 22 && variant.num_hom_alt == 0
• see using slivar for rare disease research

References:

• Pedersen, B.S., Brown, J.M., Dashnow, H. et al. Effective variant filtering and expected candidate variant yield in studies of rare human disease. npj Genom. Med. 6, 60 (2021). doi:10.1038/s41525-021-00227-3

• slivar wiki
• slivar on GitHub

• Module Name: slivar (see the modules page for more information)
• For multithreaded application of the expr subcommand only, use pslivar.
• Environment variables set
  • SLIVAR_HOME
• Developer's provided javascript expressions in $SLIVAR_HOME/js
• Example files in $SLIVAR_HOME/tests
• Reference data (pregenerated gnotation files) in /fdb/slivar/

Allocate an interactive session and run the program.
Sample session (user input in bold):

[user@biowulf]$ sinteractive
salloc.exe: Pending job allocation 46116226
salloc.exe: job 46116226 queued and waiting for resources
salloc.exe: job 46116226 has been allocated resources
salloc.exe: Granted job allocation 46116226
salloc.exe: Waiting for resource configuration
salloc.exe: Nodes cn3144 are ready for job

[user@cn3144 ~]$ module load slivar

[user@cn3144 ~]$ slivar expr \
    --js $SLIVAR_HOME/js/slivar-functions.js \
    -g /fdb/slivar/gnomad.hg38.genomes.v3.fix.zip \
    --vcf $SLIVAR_HOME/tests/ashk-trio.vcf.gz \
    --ped $SLIVAR_HOME/tests/ashk-trio.ped \
    --info "INFO.gnomad_popmax_af < 0.01 && variant.FILTER == 'PASS'" \
    --trio "example_denovo:denovo(kid, dad, mom)" \
    --family-expr "denovo:fam.every(segregating_denovo)" \
    --trio "custom:kid.het && mom.het && dad.het && kid.GQ > 20 && mom.GQ > 20 && dad.GQ > 20"  \
    --pass-only \
    -o ashk-trio.slivar.vcf

[user@cn3144 ~]$ exit
salloc.exe: Relinquishing job allocation 46116226
[user@biowulf ~]$

Create a batch input file (e.g. slivar.sh). For example:

#!/bin/bash
set -e
module load slivar
slivar expr \
  --js $SLIVAR_HOME/js/slivar-functions.js \
  -g /fdb/slivar/gnomad.hg38.genomes.v3.fix.zip \
  --vcf $SLIVAR_HOME/tests/ashk-trio.vcf.gz \
  --ped $SLIVAR_HOME/tests/ashk-trio.ped \
  --info "INFO.gnomad_popmax_af < 0.01 && variant.FILTER == 'PASS'" \
  --trio "example_denovo:denovo(kid, dad, mom)" \
  --family-expr "denovo:fam.every(segregating_denovo)" \
  --trio "custom:kid.het && mom.het && dad.het && kid.GQ > 20 && mom.GQ > 20 && dad.GQ > 20"  \
  --pass-only \
  -o ashk-trio.slivar.vcf

Submit this job using the Slurm sbatch command.

sbatch [--cpus-per-task=#] [--mem=#] slivar.sh

Create a swarmfile (e.g. slivar.swarm). For example:

slivar expr --js $SLIVAR_HOME/js/slivar-functions.js -g /fdb/slivar/gnomad.hg38.genomes.v3.fix.zip --vcf sample1.vcf --ped sample1.ped -o sample1.slivar.vcf ...
slivar expr --js $SLIVAR_HOME/js/slivar-functions.js -g /fdb/slivar/gnomad.hg38.genomes.v3.fix.zip --vcf sample2.vcf --ped sample2.ped -o sample2.slivar.vcf ...
slivar expr --js $SLIVAR_HOME/js/slivar-functions.js -g /fdb/slivar/gnomad.hg38.genomes.v3.fix.zip --vcf sample3.vcf --ped sample3.ped -o sample3.slivar.vcf ...
slivar expr --js $SLIVAR_HOME/js/slivar-functions.js -g /fdb/slivar/gnomad.hg38.genomes.v3.fix.zip --vcf sample4.vcf --ped sample4.ped -o sample4.slivar.vcf ...

Submit this job using the swarm command.

swarm -f slivar.swarm [-g #] [-t #] --module slivar