Large genomic rearrangements affecting one or more exons account for approximately 5~10% of all disease-causing mutations in BRCA1 and BRCA2 genes in patients with hereditary breast and ovarian cancer syndrome. DRAGEN LR can detect within gene large genomic rearrangements in tumor-only mode for targeted panels such as TruSight Oncology 500. The performance has been verified for BRCA1/2 with TruSight Oncology 500 Assay.
Use the following command-line options to run large rearrangement detection. The same cmd line options can be tested on other tumor-only pipelines.
--tso500-solid-brca-lr=true Set to true enable large rearrangement parameters. This is not limited to TruSight Oncology 500 Assay.
--cnv-normals-list Specify the panel of normal samples to measure instrinsic biases of the upstream processes to allow for proper normalization. To generate a panel of normals, see the example command line. The panel of normal samples should be well matched to the case sample under analysis.
--cnv-target-bed Specify the targeted regions of the panel.
--cnv-within-gene-lr-bed Specify the gene regions in BED format to do large rearrangment calling. Example file:
Run the following command on each normal sample to generate .target.counts.gc-corrected.gz file.
Put the path to the generated .target.counts.gc-corrected.gz files into a txt file. One file per line. This will be the file given to --cnv-normals-list.
The output file .cnv.LR.json contains the breakpoints detected for each specified gene region. The following is an example output file.
Note that coordinate follows BED format [start,stop) suggesting:
start: segment starting coordinate. (0-base inclusive: first base on the chromosome is numbered 0. start coordinate is included in the interval)
stop: segment stop coordinate. (0-base exclusive: first base on the chromosome is numbered 0. stop coordinate is not included in the interval)