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FusionAnalyzer

Post-processing tool for gene fusion analysis.

Warning: Do not run more than one instance of this component at a time or the database breaks. The pegasus database cannot handle more than one connection at a time. If you really need to then you need to have different pegasus installations for each one of them.

The component takes as input an Array of FusionCaller outputs. the folders must contain a file ".tool" that names the tool used, and a file "final" that is used as a data input for this component. Analyses several fusion detection tools (ChimeraScan, FusionCatcher, deFuse, SOAPfuse, EricScript, StarFusion):

ChimeraScan output file: "chimeras.bedpe" FusionCatcher output file: "final-list_candidate-fusion-genes.txt" deFuse output file: "results.tsv" or "results.filtered.tsv" or "results.classify.tsv" SOAPfuse output file: "*.final.Fusion.specific.for.genes" EricScript output file: "*.results.total.tsv" or "*.results.filtered.tsv" StarFusion output file: star-fusion.fusion_predictions.abridged.tsv

The valid values for .tool file are: "chimerascan", "fusioncatcher", "defuse", "ericscript", "soapfuse", "starfusion". You can also use the short acronyms: CS,FS,DF,ES,SF,Star

It is possible to skip the filtering step and use the csvs input to run pegasus and oncofuse. The csv array needs to have the fusions in the following format: gene1_name gene2_name ensembl_gene_id1 ensembl_gene_id2 start_position1:end_position1:gene_strand1 start_position2:end_position2:gene_strand2 chr1:bp1-chr2:bp2 span_cnt encompassing_cnt The names of the column headers do not matter, but the order has to be respected and the format for giving the gene coordinate. Calls from different tools can be merged in the same file, but each sample needs to have its own file since that is how they are submitted to pegasus. Since there is no sample column in the file, each filename will be used as sample name.

The installation of pegasus created using the installation script found in sequencing/lib allows Pegasus to run with hg38 build. It is possible that errors may have been introduced when doing this conversion, so use under your own risk.

The component consists in several steps:

1. Step1: It matches predicted fusion events (fusion detection tool outputs) according to chromosomal location and corresponding annotated gene using FusionMatcher (https://github.com/yhoogstrate/fuma), producing the overlapping set of fusion shared between samples and tools.
2. Step2: It filters out fusion candidates if: a) the number of supporting reads mapping across the fusion junction is less then "filter" parameter, b) the genes involved in the fusion are homologous, c) the genes involved in the fusion are not functionally annotated.
3. Step3: It prioritizes and annotates fusion candidates predicting their oncogenic potential using Pegasus* (https://github.com/RabadanLab/Pegasus) and Oncofuse (http://www.unav.es/genetica/oncofuse.html).
4. Step4: It combines the results of Pegasus and Oncofuse listing in the main output file only the fusions having oncogenic probability values (accordingly to Pegasus and Oncofuse) greather then the following thresholds:
   1. Pegasus oncogenic probability >= "th1" parameter
   2. Oncofuse oncogenic probability >= "th2" parameter
   3. (Pegasus oncogencic probability >= "th3" parameter) and (Oncofuse oncogenic probability >= "th4" parameter). (N.b.: th3 and th4 should be smaller then th1 and th2)

The component outputs are: A main output file containing a fusion list with high oncogenic probability (as described at step 4), and an output folder. The output folder contains:

1. "overlapping.coord.txt" produced by FusionMatcher, describing the overlapping set of fusions.
2. List of fusions that didn't pass the filtering step (SAMPLE_ID_TOOL.filtered_out.txt").
3. Oncofuse output files ("SAMPLE_ID_TOOL.oncofuse.txt).
4. Pegasus output file ("pegasus.output.txt").

$PEGASUS_HOME=Pegasus_home_directory
    java -jar $PEGASUS_HOME/jars/QueryFusionDatabase.jar -t FUSIONS_COMPLETE_ID -c deleteAll -d $PEGASUS_HOME/resources/hsqldb-2.2.7/hsqldb/mydb

Before run the compenent install the required tools (FusionMatcher, Pegasus, Oncofuse) with the respective installation scripts in $ANDURIL_HOME/bundles/sequencing/lib/install_scripts/.

Inputs

Outputs

Parameters

Test cases