> 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-somatic.md).

# DRAGEN Somatic

Select the DRAGEN Somatic 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-278caaf072205698a663484b09dde7c1108604d8%2Fimage%20(109).png?alt=media" alt=""><figcaption></figcaption></figure>

**WARNING**: Deviation from these instructions (including adding additional options) may cause pipeline failure.

1. Add "Analysis Name".
2. Select Project to "Save Results To".
3. For Pipeline Configuration, select "Map/Align + Somatic Small Variant Caller (FASTQ or BAM or CRAM input)".
4. Somatic CNV Calling
   1. This option is "None" by default. Optionally, select "Tumor-only" or "Tumor-Normal" depending on the input type.
5. Add tumor biosamples by uploading FASTQs, BAMs, or CRAMs. Optionally, add normal samples by uploading FASTQs, BAMs, or CRAMs.
   1. <mark style="color:blue;">**NOTE**</mark>: Multiple files can be uploaded at one time as long as the assigned "Sample Sex" value is the same for all samples. For example, if "Auto-Detect" is selected, it is assigned to all samples selected.
6. Select a reference, or upload a custom DRAGEN Reference File.
7. (Optional) Target BED
   1. Select a specific panel or upload a BED.
8. (Optional) Pre-built Systematic Noise BED
   1. Select a pre-built systematic noise BED or upload a BED.
9. (Optional) CNV
   1. If running CNV, unselect "Enable Cytogenetics for Allele Specific CNV Calling".
   2. Select "Enable GC Bias Correction".
10. (Optional) Structural Variants
    1. Select "Enable SV calling"
    2. Select or provide a custom SV Target BED.
    3. Provide a SV Systematic Noise BED.
11. (Optional) Small Variant Calling
    1. Select "Enable Small Variant Calling"
    2. Select "Enable Small Variant Calling on Normal Samples" if doing tumor-normal; unselect if doing tumor-only analysis.
    3. Select "Enable Common Germline Variant Tagging".
12. Methylation for Illumina 5-Base DNA Prep
    1. Select "Enable 5-Base Methylation-Aware Algorithms".
13. (Optional) Variant Annotation
    1. Select "Enable variant annotation"
14. Advanced Settings
    1. Select "Enable Duplicate Marking"
15. (Optional) Fragmentomics
    1. Select "Enable Fragmentomics"
    2. Select "Enable End Motif"
    3. Select "Enable WPS" and provide a WPS Target BED.
16. Additional Arguments
    1. (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.
    2. (Optional) Under Additional DRAGEN Command Line Arguments, add `--enable-fractional-down-sampler=true --down-sampler-tumor-subsample=$Fraction` to enable downsampling, where $Fraction is a value between 0 and 1 representing the proportion of reads to keep. For tumor-normal analyses, use `--down-sampler-normal-subsample` for the normal sample.
    3. (Optional) Under Additional DRAGEN Command Line Arguments, add `--gc-metrics-enable=true` to enable GC metrics.


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