While DRAGEN secondary analysis is capable of supporting up to 1000x coverage, its default settings are tuned for a more typical sample size in the ~100x range. So if you find that the processing of your large sample doesn't complete, or gives unexpected results, there are options available to improve the behavior.
Users may want to analyze high amounts of data using the DRAGEN secondary analysis. For instance, in somatic contexts it can be beneficial to sequence the tumor at a very high depth to detect mutations at even lower frequencies. DRAGEN reliably supports a total average coverage of up to 1000x. As the input read data can grow excessively, but the system memory is limited, DRAGEN can only keep a subset of the input in RAM at the same time. The area reserved for the read data is called bin_memory. Higher bin_memory size means that bigger chunks can be processed simultaneously, but less memory is available to the rest of DRAGEN or for other processes.
After the map-align step, reads are loaded into the bin_memory, looking for regions of zero coverage. A set of reads that spans two such zero-coverage loci is a callable region. The memory used by a callable region is determined by the number of reads and their length. For instance, a long region with few reads per position uses the same amount of memory as a short region with a spike in coverage. The size of a callable region must stay well below the size of the bin_memory. To this end, any callable region that surpasses the --vc-max-callable-region-memory-usage
threshold is cut into smaller regions. Due to these cuts, the accuracy of variant calls in the vicinity may be affected.
The following options can be used to change the bin_memory and callable region size.
--bin_memory
Set the amount of memory reserved for read data. Defaults to at least 20GB for germline and 40GB for a somatic run.
--vc-max-callable-region-memory-usage
Set the maximum size of a single callable region. Default is 13GB.