Genome Nexus Annotation Pipeline

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

MAF Annotation

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>

You can choose to replace the gene symbols in the new maf by the gene symbols found by Genome Nexus by supplying the -r optional parameter. 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.

Annotate data with Docker

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

Usage instruction

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.

Optional parameters

Short	Long	Description
-h	--help	shows this help document and quits
-f	--filename	Mutation filename
-o	--output-filename	Output filename (including path)
-t	--output-format	extended, minimal or a file path which includes output format (FORMAT EXAMPLE: Chromosome,Hugo_Symbol,Entrez_Gene_Id,Center,NCBI_Build)
-i	--isoform-override	Isoform Overrides. Options: mskcc or uniprot
-e	--error-report-location	Error report filename (including path)
-r	--replace-symbol-entrez	Replace gene symbols and entrez id with what is provided by annotator"
-p	--post-interval-size	Number of records to make POST requests to Genome Nexus with at a time
-s	--strip-matching-bases	Strip matching allele bases. Options: first, all, none. For example: AAC/AAT, strip-off first: AC/AT, strip-off all: C/T, strip-off none: AAC/AAT
-a	--add-original-genomic-location	Add original genomic location data columns into the output, name columns with prefix 'IGNORE_Genome_Nexus_Original_'). This would be useful if saving a reference of original input is needed and won't be changed in any condition
-d	--ignore-original-location	Genome-nexus-annotation-pipeline reads original genomic location info as input by default, if not existing, reading from normal genomic location info columns. Adding -d ignores original genomic location info columns (columns with prefix 'IGNORE_Genome_Nexus_Original_') and only use whatever in normal genomic location info columns. This would be helpful if you'd like to stick with current genomic location info columns.

Minimal MAF Example

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

Direct Database Annotation

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.

Annotator

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.

Updating the Genome Nexus Annotation Pipeline

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.