Biowulf High Performance Computing at the NIH
Exomiser on Biowulf

The Exomiser is a Java program that finds potential disease-causing variants from whole-exome or whole-genome sequencing data.

Starting from a VCF file and a set of phenotypes encoded using the Human Phenotype Ontology (HPO) it will annotate, filter and prioritise likely causative variants. The program does this based on user-defined criteria such as a variant's predicted pathogenicity, frequency of occurrence in a population and also how closely the given phenotype matches the known phenotype of diseased genes from human and model organism data.

The functional annotation of variants is handled by Jannovar and uses UCSC KnownGene transcript definitions and hg19 genomic coordinates.

Variants are prioritised according to user-defined criteria on variant frequency, pathogenicity, quality, inheritance pattern, and model organism phenotype data. Predicted pathogenicity data is extracted from the dbNSFP resource. Variant frequency data is taken from the 1000 Genomes, ESP and ExAC datasets. Subsets of these frequency and pathogenicity data can be defined to further tune the analysis. Cross-species phenotype comparisons come from our PhenoDigm tool powered by the OWLTools OWLSim algorithm.


Important Notes

Interactive job
Interactive jobs should be used for debugging, graphics, or applications that cannot be run as batch jobs.

Allocate an interactive session and run the program. Sample session:

[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 exomiser
[user@cn3144 ~]$ mkdir /data/$USER/exomiser
[user@cn3144 ~]$ cd /data/$USER/exomiser
[user@cn3144 ~]$ cp -rp /usr/local/apps/exomiser/9.0.0/examples .
[user@cn3144 ~]$ cp /usr/local/apps/exomiser/9.0.0/ .
[user@cn3144 ~]$ mkdir results
[user@cn3144 ~]$ java -Xms2g -Xmx4g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml

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

Batch job
Most jobs should be run as batch jobs.

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

set -e
module load exomiser
cd /data/$USER/..........

java -Xms2g -Xmx10g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml

NOTE: -Xmx10g is depend on how much memory is requested when submitting the job below. For example, if 10g of memory is requested, then put 10g here.

Submit this job using the Slurm sbatch command.

sbatch --mem=10g --cpus-per-task=40
Swarm of Jobs
A swarm of jobs is an easy way to submit a set of independent commands requiring identical resources.

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

cd dir1;java -Xms2g -Xmx10g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml
cd dir2;java -Xms2g -Xmx10g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml
cd dir3;java -Xms2g -Xmx10g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml
cd dir4;java -Xms2g -Xmx10g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml
cd dir5;java -Xms2g -Xmx10g -jar $EXOMISERJAR --analysis examples/test-analysis-exome.yml

Submit this job using the swarm command.

swarm -f exomiser.swarm -g 10 -t 40 --module exomiser
-g # Number of Gigabytes of memory required for each process (1 line in the swarm command file)
-t # Number of threads required for each process (usually use 40)
--module exomiser Loads the vcftools module for each subjob in the swarm