> For the complete documentation index, see [llms.txt](https://help.bioinsight.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.bioinsight.illumina.com/dragen-5-base/run-analysis-setup/ica-analysis-setup/dragen-somatic-whole-genome/dragen-somatic-enrichment.md).

# 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:

* Liquid UMI
  * Post-Collapsed Coverage Rate above 2000x
* Solid UMI
  * Post-Collapsed Coverage Rate 200-2000x
* Low Coverage
  * Coverage Rate below 200x

**Set the minimum supporting reads to 2 for liquid UMI and to 1 for solid UMI.**

1. Select the necessary input files for the run, including Tumor and Normal inputs (.fastq.gz, .fastq.ora, .bam, or .cram files).
2. Select a reference genome. 5-base is compatible with any methyl\_cg reference. One recommendation is the Homo sapiens \[1000 Genomes] hg38 v6 Pangenome reference.
3. (Optional) Select a target BED file.
4. Map/Align Options
   1. Select "Enable Map/Align".
   2. If running with liquid or solid UMIs, unselect "Enable Duplicate Marking". If running at low coverage, select "Enable Duplicate Marking".
5. (Optional) Small Variant Caller Options
   1. Select "Enable Small Variant Caller".
   2. Select a Pre-built systematic noise BED.
   3. Select "Enable Germline Tagging".
6. CNV Caller Options
   1. Unselect "Enable CNV Calling".
7. (Optional) SV Caller Options (compatible with tumor-only)
   1. Select "Enable SV Calling".
   2. Select a SV Target BED or provide a custom file.
   3. Provide a custom SV Systematic Noise BED.
8. (Optional) Variant Annotation Options
   1. Select "Enable Variant Annotation".
9. Methylation Options
   1. Select "Enable 5-Base Methylation-Aware Algorithms".
10. UMI Options
    1. For liquid UMI analyses
       1. Select "Enable UMI".
       2. Select "Nonrandom-duplex" for UMI Library Type.
       3. Set UMI Aware Variant Calling to "High depth".
       4. Set Minimum Supporting UMI reads to "2".
    2. For solid UMI analyses
       1. Select "Enable UMI".
       2. Select "Nonrandom-duplex" for UMI Library Type.
       3. Set UMI Aware Variant Calling to "Low depth".
       4. Set Minimum Supporting UMI reads to "1".
    3. For low coverage analyses
       1. Do not select "Enable UMI".
11. (Optional) Fragmentomics
    1. Select "Enable Fragmentomics".
    2. Select "Enable End Motif".
    3. Select "Enable WPS" and provide a target BED file.
12. (Optional) Advanced Options
    1. Under Additional DRAGEN Command Line Arguments, add `--qc-coverage-ignore-overlaps=true`.
    2. Under Additional DRAGEN Command Line Arguments, 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.
    3. Select "Enable Germline Variant Caller on Normal" if doing tumor-normal; unselect if doing tumor-only analysis.
13. Start the analysis


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