Running Exomiser

Usage

In general we recommend running Exomiser from the install directory. A single sample exome analysis can be run using the following command:

# run a test exome analysis
cd exomiser-cli-14.0.0
java -jar exomiser-cli-14.0.0.jar --sample examples/pfeiffer-phenopacket.yml --vcf examples/Pfeiffer.vcf.gz --assembly hg19

This command prioritises variants from the input VCF file, called against the GRCh37/hg19 reference assembly in the context of the sample phenotypes encoded using Human Phenotype Ontology terms contained in the Phenopacket file.

Running a multi-sample VCF for trios also requires a PED file. e.g.

# run a test exome family analysis
cd exomiser-cli-14.0.0
java -jar exomiser-cli-14.0.0.jar --sample examples/pfeiffer-family.yml --vcf examples/Pfeiffer-quartet.vcf.gz --assembly hg19 --ped examples/Pfeiffer-quartet.ped

By default there will be two output files written to the results directory using the same filename as the input VCF file but with _exomiser appended before a file extension of .json or .html e.g.

ls results/Pfeiffer*
results/Pfeiffer_exomiser.html  results/Pfeiffer_exomiser.json

The HTML file is for human use, whilst the JSON file is better read by machines, for instance by using jq. Details on how to interpret the output can be found in the Interpreting the Results section.

The examples directory contains a selection of single sample exome and genome analysis files, a multisample (family) analysis with an associated pedigree in PED format, and the respective Phenopacket representations of the proband or family.

Want help?

java -jar exomiser-cli-14.0.0.jar --help

Running from alternate directory

If you’re running the exomiser from a different directory to the one the exomiser-cli-14.0.0.jar file is located, you will need to specify the path to the application.properties file in the start-up command. For example:

java -Xmx4g -jar /full/path/to/your/exomiser-cli/directory/exomiser-cli-14.0.0.jar --analysis /full/path/to/your/exomiser-cli/directory/examples/test-analysis-exome.yml --spring.config.location=/full/path/to/your/exomiser-cli/directory/application.properties

n.b. the spring.config.location command must be the last argument in the input commands!

Troubleshooting

java.lang.UnsupportedClassVersionError:

If you get the following error message:

Exception in thread "main" java.lang.UnsupportedClassVersionError:
org/monarchinitiative/exomiser/cli/Main : Unsupported major.minor version

or

Error: A JNI error has occurred, please check your installation and try again
Exception in thread "main" java.lang.UnsupportedClassVersionError: org/monarchinitiative/exomiser/cli/Main has been
compiled by a more recent version of the Java Runtime (class file version 55.0), this version of the Java Runtime
only recognizes class file versions up to 52.0

You are running an older unsupported version of Java. Exomiser requires java version 17 or higher. This can be checked by running:

$ java -version

You should see something like this in response:

openjdk version "17.0.9" 2023-10-17
OpenJDK Runtime Environment (build 17.0.9+9-Ubuntu-122.04)
OpenJDK 64-Bit Server VM (build 17.0.9+9-Ubuntu-122.04, mixed mode, sharing)

Versions lower than 17 (e.g. 1.5, 1.6, 1.7, 1.8, 9, 10) will not run exomiser, so you will need to install the latest java version.