See Installation for getting software and then the Usage section for info on running an analysis.

Message from @snewhouse: I have this here for convenience as https://exomiser.github.io/Exomiser/ installation instructions is a little out of date.

This is the README.md from http://data.monarchinitiative.org/exomiser/ where the latest version of Exomiser is hosted.

../
10.0.0/                                            07-Mar-2018 16:08                   -
10.0.1/                                            20-Mar-2018 15:40                   -
10.1.0/                                            18-May-2018 09:46                   -
6.0.0/                                             06-Feb-2017 22:04                   -
7.2.1/                                             08-Aug-2017 10:32                   -
8.0.0/                                             11-Dec-2017 13:47                   -
9.0.0/                                             12-Dec-2017 17:09                   -
9.0.1/                                             15-Jan-2018 12:17                   -
data/                                              12-Jul-2018 09:22                   -
latest/                                            12-Jul-2018 09:26                   -
README.md                                          24-Jan-2018 09:56               10567

All credit goes to the orginal developers.

citations

Damian Smedley, Max Schubach, Julius OB Jacobsen, Sebastian Köhler, Tomasz Zemojtel, Malte Spielmann, Marten Jäger, Harry Hochheiser, Nicole L Washington, Julie A McMurry, Melissa A Haendel, Christopher J Mungall, Suzanna E Lewis, Tudor Groza, Giorgio Valentini, Peter N Robinson. (2016).

A Whole-Genome Analysis Framework for Effective Identification of Pathogenic Regulatory Variants in Mendelian Disease. The American Journal of Human Genetics, 99(3), 595–606. http://doi.org/10.1016/j.ajhg.2016.07.005

This tool rocks! 🤘

The Exomiser is a tool to perform genome-wide prioritisation of genomic variants including non-coding and regulatory variants using patient phenotypes as a means of differentiating candidate genes.

To perform ana analysis, Exomiser requires the patient's genome/exome in VCF format and their phenotype encoded in HPO terms. The exomiser is also capable of analysing trios/small family genomes, so long as a pedigree in PED format is also provided. See Usage section for info on running an analysis.

Further information can be found in the online documentation.

• For exome analysis of a 30,000 variant sample 4GB RAM should suffice.
• For genome analysis of a 4,400,000 variant sample 12GB RAM should suffice.
• Any 64-bit operating system
• Java 8 or above
• At least 50GB free disk space (SSD preferred for best performance)
• An internet connection is not required to run the Exomiser, although network access will be required if accessing a networked database (optional).
• By default the Exomiser is completely self-contained and is able to run on standard consumer laptops.

​

1. Install 7-Zip (http://www.7-zip.org) for unzipping the archive files. The built-in archiving software has issues extracting the zip files.
2. Download the data and distribution files from https://data.monarchinitiative.org/exomiser/latest
3. Extract the distribution files by right-clicking exomiser-cli-9.0.1-distribution.zip and selecting 7-Zip > Extract Here
4. Extract the data files (e.g. 1711_phenotype.zip, 1711_hg19.zip) by right-clicking the archive and selecting 7-Zip > Extract files... 4.1 Extract the files to the exomiser data directory. By default exomiser expects this to be exomiser-cli-9.0.1/data, but this can be changed in the application.properties
5. cd exomiser-cli-9.0.1
6. java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --analysis examples/test-analysis-exome.yml

The following shell script should work- ​

#download the distribution (won't take long)
wget https://data.monarchinitiative.org/exomiser/latest/exomiser-cli-9.0.1-distribution.zip
#download the data (this is ~20GB and will take a while)
wget https://data.monarchinitiative.org/exomiser/latest/1711_hg19.zip
wget https://data.monarchinitiative.org/exomiser/latest/1711_hg38.zip
wget https://data.monarchinitiative.org/exomiser/latest/1711_phenotype.zip

#unzip the distribution and data files - this will create a directory called 'exomiser-cli-9.0.1' in the current working directory
unzip exomiser-cli-9.0.1-distribution.zip
unzip 1711_*.zip -d exomiser-cli-9.0.1/data

#Check the application.properties are pointing to the correct versions
#exomiser.hg19.data-version=1711
#exomiser.hg38.data-version=1711
#exomiser.phenotype.data-version=1711

#run a test genomiser analysis
cd exomiser-cli-9.0.1
java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --analysis examples/test-analysis-exome.yml

This script will download, verify and extract the exomiser files and then run the analysis contained in the file 'test-analysis-exome.yml' from the examples sub-directory. This contains a known pathogenic missense variant in the FGFR2 gene.

In order to run the Genomiser you will also need to download the REMM data file from here. Once downloaded you'll need to add the path to the ReMM.v0.3.1.tsv.gz file to the application.properties file. For example if you downloaded the file to the exomiser data directory you could add the entry like this:

exomiser.hg19.remm-path=${exomiser.hg19.data-directory}/ReMM.v0.3.1.tsv.gz

If this step is omitted, the application will throw and error and stop any analysis which defines REMM in the pathogenicitySources section of an analysis yml file.

Having done this, run the analysis like this:

java -Xms4g -Xmx6g -jar exomiser-cli-9.0.1.jar --analysis examples/NA19722_601952_AUTOSOMAL_RECESSIVE_POMP_13_29233225_5UTR_38.yml 

This is an analysis for an autosomal recessive 5'UTR variant located in POMP gene on chromosome 13. The phenotype HPO terms are taken from the clinical synopsis of OMIM #601952 (http://www.omim.org/clinicalSynopsis/601952)

If you want to run Exomiser using data from a different release directory edit the line in application.properties:

exomiser.data-directory=

with

exomiser.data-directory=/full/path/to/alternative/data/directory

The Exomiser can be run via simply via command line switches (see cli only) or via a yaml analysis file. We strongly recommended using the yaml option as it provides full control over the application. The cli only options are currently a legacy hangover only capable of exome analysis.

Analysis files contain all possible options for running an analysis including the ability to specify variant frequency and pathogenicity data sources and the ability to tweak the order that analysis steps are performed.

See the test-analysis-exome.yml and test-analysis-genome.yml files located in the base install directory for details.

java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --analysis examples/test-analysis-exome.yml

These files an also be used to run full-genomes, however they will require substantially more RAM to do so. For example a 4.4 million variant analysis requires approximately 12GB RAM. However, RAM requirements can be greatly reduced by setting the analysisMode option to PASS_ONLY. This will also aid your ability to evaluate the results.

Analyses can be run in batch mode. Simply put the path to each analysis file in the batch file - one file path per line.

java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --analysis-batch examples/test-analysis-batch.txt

(a) Exomiser hiPHIVE algorithm - phenotype comparisons to human, mouse and fish involving disruption of the gene or nearby genes in the interactome using a RandomWalk

java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --prioritiser=hiphive -I AD -F 1 -D OMIM:101600 -v data/Pfeiffer.vcf

java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --prioritiser=hiphive -I AD -F 1 --hpo-ids HP:0000006,HP:0000174,HP:0000194,HP:0000218,HP:0000238,HP:0000244,HP:0000272,HP:0000303,HP:0000316,HP:0000322,HP:0000324,HP:0000327,HP:0000348,HP:0000431,HP:0000452,HP:0000453,HP:0000470,HP:0000486,HP:0000494,HP:0000508,HP:0000586,HP:0000678,HP:0001156,HP:0001249,HP:0002308,HP:0002676,HP:0002780,HP:0003041,HP:0003070,HP:0003196,HP:0003272,HP:0003307,HP:0003795,HP:0004209,HP:0004322,HP:0004440,HP:0005048,HP:0005280,HP:0005347,HP:0006101,HP:0006110,HP:0009602,HP:0009773,HP:0010055,HP:0010669,HP:0011304 -v data/Pfeiffer.vcf

(b) Exomiser PHIVE algorithm - phenotype comparisons to mice with disruption of the gene

java -Xmx2g -jar exomiser-cli-9.0.1.jar --prioritiser=phive -I AD -F 1 -D OMIM:101600 -v data/Pfeiffer.vcf

(c) Exomiser Phenix algorithm - phenotype comparisons to known human disease genes

java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --prioritiser=phenix -v data/Pfeiffer.vcf -I AD -F 1 --hpo-ids HP:0000006,HP:0000174,HP:0000194,HP:0000218,HP:0000238,HP:0000244,HP:0000272,HP:0000303,HP:0000316,HP:0000322,HP:0000324,HP:0000327,HP:0000348,HP:0000431,HP:0000452,HP:0000453,HP:0000470,HP:0000486,HP:0000494,HP:0000508,HP:0000586,HP:0000678,HP:0001156,HP:0001249,HP:0002308,HP:0002676,HP:0002780,HP:0003041,HP:0003070,HP:0003196,HP:0003272,HP:0003307,HP:0003795,HP:0004209,HP:0004322,HP:0004440,HP:0005048,HP:0005280,HP:0005347,HP:0006101,HP:0006110,HP:0009602,HP:0009773,HP:0010055,HP:0010669,HP:0011304

(d) Exomiser ExomeWalker algorithm - prioritisation by proximity in interactome to the seed genes

java -Xms2g -Xmx4g -jar exomiser-cli-9.0.1.jar --prioritiser exomewalker  -v data/Pfeiffer.vcf -I AD -F 1 -S 2260

--output-format HTML (default)
--output-format TSV-GENE (TSV summary of genes)
--output-format TSV-VARIANT (TSV summary of variants)
--output-format VCF (VCF summary)

Output options can be combined, for example:

--output-format TSV-GENE,VCF (TSV-GENE and VCF)
--output-format TSV-GENE, TSV-VARIANT, VCF (TSV-GENE, TSV-VARIANT and VCF)

This feature is now deprecated and may be subject to removal at a later time. We recommend switching to using an analysis yml file instead. ​

java -jar exomiser-cli-9.0.1.jar --help

If you get the following error message:

Exception in thread "main" java.lang.UnsupportedClassVersionError:
de/charite/compbio/exomiser/cli/Main : Unsupported major.minor version

You are running an older unsupported version of Java. Exomiser requires java version 8 or higher. This can be checked by running: ​

java -version

You should see something like this in response: ​

java version "1.8.0_65"

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

If, when running unzip 'exomiser-cli-9.0.1-distribution.zip', you see the following: ​

error:  Zip file too big (greater than 4294959102 bytes)
Archive:  exomiser-cli-9.0.1-distribution.zip
warning [exomiser-cli-9.0.1-distribution.zip]:  9940454202 extra bytes at beginning or within zipfile
  (attempting to process anyway)
error [exomiser-cli-9.0.1-distribution.zip]:  start of central directory not found;
  zipfile corrupt.
  (please check that you have transferred or created the zipfile in the
  appropriate BINARY mode and that you have compiled UnZip properly)

Check that your unzip version was compiled with LARGE_FILE_SUPPORT and ZIP64_SUPPORT. This is standard with UnZip 6.00 and can be checked by typing: ​

unzip -version

This shouldn't be an issue with more recent linux distributions.