# DRAGEN Somatic (Enrichment)
**WARNING**: Deviation from these instructions (including adding additional options) may cause pipeline failure.
### Coverage Rate Minimums
The following coverage rates are the minimums recommended for each of the various workflows:
* High Coverage
* Post-Collapsed Coverage Rate >2000x (liquid tumor mode)
* Medium Coverage
* Post-Collapsed Coverage Rate 200-300x (solid tumor mode)
* Low Coverage
* Coverage Rate >100x for Somatic Methyl + VC
**If the UMI-collapsed reads do not meet the recommended post-collapsed coverage depths for the solid tumor or liquid biopsy pipelines, then it is recommended to run with the default UMI settings.**
1. Select the necessary input files for the run, including sample inputs (.fastq, .fastq.ora, .bam, or .cram files), a Target BED File, and a Baseline Systematic Noise Filter BED File.
2. Select a reference genome. 5-base is compatible with any methyl\_cg reference. One recommendation is the Homo sapiens \[1000 Genomes] hg38 v5 Pangenome reference.
1. A graph reference is recommended for Germline and non-graph is the recommendation for Somatic.
3. To Enable Methylation Aware Algorithms, check the box for Enable 5-Base Methylation-Aware Algorithms.
4. For Report Methylation at Variant Positions, select "default".
5. In the Variant Calling Options section:
1. Set Emit Ref Confidence to "GVCF".
2. Set VCF File Output to "True".
3. Set Enable Germline Tagging to "False".
4. Set Enable CNV calling to "False".
5. Set CNV GC Bias Correction to "False".
6. Set Enable Allele-Specific CNV Calling to "False".
7. Set Enable SV Caller to "False".
6. In the UMI Options section:
1. If running high or medium coverage, set Enable UMI to "True". If running low coverage, set Enable UMI to "False".
2. If running high or medium coverage, set UMI Library Type to "nonrandom-duplex".
3. If running high coverage, set UMI Aware Variant Calling to "High depth". If running medium coverage, set UMI Aware Variant Calling to "Low depth".
4. If running high coverage, set Minimum Supporting UMI reads to "2". If running medium coverage, set Minimum Supporting UMI reads to "1".
 
7. If running high or medium coverage, set Enable Variant Annotation to "True".\
8. In the Advanced Options section, under Additional DRAGEN Args,
1. If running low coverage, add `--vc-systematic-noise-method=mean` and `--enable-duplicate-marketing=true`.
2. (Optional): Add `--qc-coverage-ignore-overlaps=true`.
3. (Optional) If running cfDNA samples, it's recommended to add `--mbias-report-include-overlaps=true` to ensure the M-bias report captures the full R2 read-cycle profile. This is important for cfDNA since the short fragments cause most of R2 to overlap R1 and be excluded from bias statistics by default.
9. Start the analysis
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