> 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/bssh-analysis-setup/dragen-enrichment.md).

# DRAGEN Enrichment

Select the DRAGEN Enrichment v4.6.2 application.

<figure><img src="https://707781091-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FL2tTN7buOERM9NKPYYlg%2Fuploads%2Fgit-blob-06c4f1570255f76450123281e55294969a2d8017%2Fimage%20(122).png?alt=media" alt=""><figcaption></figcaption></figure>

**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. Add "Analysis Name".
2. Select Project to "Save Results To".
3. Add biosamples by uploading FASTQs, BAMs, or CRAMs.
   1. Sample Sex should be "Auto Detect".
4. Variant Caller Mode
   1. Select "Germline" or "Somatic".
5. Select a reference, or upload a custom DRAGEN Reference File.
6. (Optional) Targeted Regions
   1. Select a specific panel or upload a BED.
7. (Optional) Structural Variants
   1. Select "Enable SV calling" and add any relevant BED files.\ <mark style="color:blue;">**NOTE:**</mark> SV Calling is formally supported for whole genome, but is an experimental feature for enrichment use cases.
8. Methylation for Illumina 5-Base DNA Prep
   1. Select "Enable 5-Base Methylation-Aware Algorithms".
9. For liquid UMI samples (post-collapsed coverage rate above 2000x) in Somatic Variant Caller Mode:
   1. Somatic Variant Calling
      1. Select a pre-built systematic noise BED or upload a custom systematic noise BED.
      2. Select "Enable Common Germline Variant Tagging".
   2. UMI Settings
      1. Select "Enable UMI".
      2. UMI Library Type should be set to "Nonrandom-duplex".
      3. Set UMI-Aware Variant Calling to "High depth".
      4. Set UMI Min Supported Reads to "2".
   3. (Optional) Variant Annotation
      1. Select "Enable Variant Annotation".
   4. Advanced Settings
      1. Pipeline Configuration must be set to "Map/Align + Variant Caller"
      2. For QC Coverage Calculation, select "Ignore Overlapping Mates".
      3. Unselect "Enable Duplicate Marking".
10. For solid UMI samples (post-collapsed coverage rate 200-2000x) using Somatic Variant Caller Mode:
    1. Somatic Variant Calling
       1. Select a pre-built systematic noise BED or upload a custom systematic noise BED.
       2. Select "Enable Common Germline Variant Tagging".
    2. UMI Settings
       1. Select "Enable UMI".
       2. UMI Library Type should be set to "Nonrandom-duplex".
       3. Set UMI-Aware Variant Calling to "Low depth".
       4. Set UMI Min Supported Reads to "1".
    3. (Optional) Variant Annotation
       1. Select "Enable Variant Annotation".
    4. Advanced Settings
       1. Pipeline Configuration must be set to "Map/Align + Variant Caller"
       2. For QC Coverage Calculation, select "Ignore Overlapping Mates".
       3. Unselect "Enable Duplicate Marking".
11. For low coverage samples (coverage rate below 200x) using Somatic Variant Caller Mode:
    1. Somatic Variant Calling
       1. Select a pre-built systematic noise BED or upload a custom systematic noise BED.
    2. Advanced Settings
       1. Pipeline Configuration must be set to "Map/Align + Variant Caller"
       2. For QC Coverage Calculation, select "Ignore Overlapping Mates".
       3. Select "Enable Duplicate Marking".
12. (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.<br>


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