These tools allow for annotation of genomic variants from a MAF for import into the cBioPortal using Genome Nexus.

The annotationPipeline module is a command line tool to annotate a maf using genome nexus.

Pre-build steps

Create your application.properties:

cp annotationPipeline/src/main/resources/application.properties.EXAMPLE annotationPipeline/src/main/resources/application.properties

If you have your own installation of Genome Nexus, you can point to it by modifying the application.properties file located in annotationPipeline/src/main/resources.

Create your log4j.properties:

cp annotationPipeline/src/main/resources/log4j.properties.EXAMPLE annotationPipeline/src/main/resources/log4j.properties

Modify the property log4j.appender.a.File in your log4j.properties file to the desired log file path.

To use it, build the project using maven and run it like so:

mvn clean install
$JAVA_HOME/bin/java -jar annotationPipeline/target/annotationPipeline-*.jar \
    --filename <INPUT_MAF> \
    --output-filename <OUTPUT DESTINATION> \
    --isoform-override <mskcc or uniprot>

To output error reporting to a file, supply the -e option a location for the file to be saved. By running the jar without any arguments or by providing the optional parameter -h you can view the full usage statement.

Genome Nexus Annotation Pipeline is available on Docker: https://hub.docker.com/r/genomenexus/gn-annotation-pipeline.

docker run -v ${PWD}:/wd genomenexus/gn-annotation-pipeline:master --filename /wd/input.txt  --output-filename /wd/output.txt

• -v ${PWD}:/wd: This option maps the current working directory to a volume within the Docker container at the path /wd. This makes it possible for files in the host directory to be accessed and modified between container and host.

• --filename /wd/input.txt: This option specifies the input file location at /wd/input.txt, which should be under the same directory as output file.

• --output-filename /wd/output.txt: This option specifies the output file where the annotated results will be saved. The file will be created at /wd/output.txt, which should be under the same directory as input file.

To enable logging in the Genome Nexus Annotation Pipeline and access the log file, you need to mount your local path to view the log file locally. By default, the log file is stored at /genome-nexus-annotation-pipeline/logs/genome-nexus-annotation-pipeline.log. Use the following command as an example:

docker run  -v ${PWD}:/wd -v ${PWD}/logs:/genome-nexus-annotation-pipeline/logs gn-annotation-pipeline:master --filename  /wd/input.txt  --output-filename /wd/output.txt

• -v ${PWD}/logs:/genome-nexus-annotation-pipeline/logs flag mounts the logs directory inside the current working directory to the corresponding directory inside the Docker container.
• Other flags are the same as above

Make sure to adjust the file paths according to your specific requirements. Once the command is executed, the log file will be generated and stored in the logs directory within your local directory.

The Genome Nexus Annotation Pipeline supports two versions of the human genome reference assembly: GRCh37 and GRCh38. By default, the pipeline uses GRCh37.

If you want to annotate with GRCh38, please set the GENOMENEXUS_BASE environment variable to https://grch38.genomenexus.org. Here's an example of how to do this:

docker run -e GENOMENEXUS_BASE=https://grch38.genomenexus.org -v ${PWD}:/wd genomenexus/gn-annotation-pipeline:latest --filename /wd/input.txt  --output-filename /wd/output.txt --isoform-override uniprot

Genome Nexus supports additional annotation columns with the setting of "enrichment_fields". The configuration for these enrichment fields is managed through the application.properties file, please refer to Pre-build steps section. To configure the enrichment fields, you need to include the desired field names from the provided list in the -Dgenomenexus.enrichment_fields= parameter of the command line, or directly add field names in genomenexus.enrichment_fields= in application.properties file. Multiple field names can be specified by separating them with commas. annotation_summary is highly recommended to add as default since it's crucial for lots of annotation fields. Example:

java 
-Dgenomenexus.enrichment_fields=annotation_summary,my_variant_info 
-jar annotationPipeline/target/annotationPipeline-*.jar \ -r \ 
--filename test/data/minimal_example.in.txt \ 
--output-filename test/data/minimal_example.out.uniprot.txt \ 
--isoform-override uniprot

• annotation_summary:
  • This field is essential for most annotation processes.
• my_variant_info
  • This field provides gnomAD information. Genome Nexus caches static myvariant.info annotation into database. Upon adding my_variant_info to the enrichment_fields, Genome Nexus will query the existing variant information from the myvariant.info cache within the database for relevant variants. For new variants, Genome Nexus will retrieve the data from myvariant.info and store it in the database.
• polyphen
• sift
• mutation_assessor
  • 'mutation_assessor' provides V3 version annotation from Mutation Assessor, which is currently stored in Genome Nexus database
• nucleotide_context
• oncokb:
  • 'oncokb' provides annotations of the biological consequences and clinical implications from OncoKB website. OncoKB token is required (see more information from: https://www.oncokb.org/apiAccess). Please also provide your token in -Doncokb.token=abc123 command line parameter, or directly add oncokb.token=abc123in the application.properties. No OncoKB annotation columns will be added if no valid token is provided

For an example minimal input file see test/data/minimal_example.in.txt and corresponding output test/data/minimal_example.out.uniprot.txt. The output file was generated with:

$JAVA_HOME/bin/java -jar annotationPipeline/target/annotationPipeline-*.jar \
    -r \
    --filename test/data/minimal_example.in.txt  \
    --output-filename test/data/minimal_example.out.uniprot.txt \
    --isoform-override uniprot

If you have data already loaded into a cBioPortal database but did not properly annotate it or discovered issues later, you can use the databaseAnnotator utility to fix it.

You will need to specify some database connection parameters inside the application.properties file located in databaseAnnotator/src/main/resources. Once this is done, build the project using maven and run like so:

$JAVA_HOME/bin/java -jar databaseAnnotator/target/databaseAnnotator-*.jar \
    --isoform <mskcc or uniprot>

As with the above tool, running the jar without any arguments or by providing the optional parameter -h will bring up the full usage statement. You can also specify a single study or set of studies to annotate by using the --studies parameter.

The annotator module is the client code that makes calls to the Genome Nexus server and interprets the response. The other two modules use this as a dependency.

The annotation pipeline uses models brought in by the auto-generated genome-nexus-java-api-client here and here .

In the event of an update to the Genome Nexus server (e.g adding to an existing model), the genome-nexus-java-api-client must be regenerated and propagated to this codebase. To generate the newest genome-nexus-java-api-client, refer to instructions here.

Once updated, update the pom with the newest commit hash from the genome-nexus-java-api-client codebase.