# DRAGEN Somatic (Whole Genome)

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

1. Select the necessary input files for the run, including Tumor and Normal inputs (.fastq, .fastq.ora, .bam, or .cram files) 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.<br>

      <figure><img src="/files/MY1KCiKVDMkOIAbhKQ6R" alt=""><figcaption></figcaption></figure>
3. To Enable Methylation Aware Algorithms, check the box for Enable 5-Base Methylation-Aware Algorithms.<br>

   <figure><img src="/files/ssqNeVnd8qsYlAugAxDT" alt=""><figcaption></figcaption></figure>
4. (Optional, if performing tumor-normal analysis only) Set Enable Germline Variant Calling On Normal Sample to "True".<br>

   <figure><img src="/files/jYAgMu4FabpwaZM9dL2T" alt=""><figcaption></figcaption></figure>
5. For Report Methylation at Variant Positions, select "default".<br>

   <figure><img src="/files/ODlTYIrh9pMAn9hsY2uX" alt=""><figcaption></figcaption></figure>
6. (Optional) To perform Small Variant Calling:
   1. Set Enable Small Variant Caller to "True"
   2. Set Emit Ref Confidence to "GVCF"
   3. Set Enable VCF File Output to "True".
   4. Set Enable Germline Tagging to "True".

      <figure><img src="/files/SrKLR2YAlu8oowVVypTA" alt="" width="563"><figcaption></figcaption></figure>
7. In the UMI Options section:
   1. Set Enable UMI to false.
   2. Click the "X" next to UMI Library Type (screenshot displays the button to click; the box will disappear upon selecting).
   3. Click the "X" next to UMI Aware Variant Calling (screenshot displays the button to click; the box will disappear upon selecting).
   4. Click the "X" next to Minimum Supporting UMI Reads (screenshot displays the button to click; the box will disappear upon selecting).<br>

      <figure><img src="/files/vAjh1bmHDHdxheP0WLNL" alt="" width="563"><figcaption></figcaption></figure>
8. In the Variant Annotation Options section:
   1. Set Enable Variant Annotation to true<br>

      <figure><img src="/files/BKcRBXXVvf1RD9GqURgH" alt="" width="563"><figcaption></figcaption></figure>
9. In the Additional Options section:
   1. (Optional) If downsampling is required, add `--enable-down-sampler=true --down-sampler-fragments=$Number_of_Reads`.

      <figure><img src="/files/Ow4leSpwQaBKY6s4x7Ik" alt=""><figcaption></figcaption></figure>
   2. (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.
10. Start the analysis.


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