> For the complete documentation index, see [llms.txt](https://help.connected.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.connected.illumina.com/dragen/dragen-v4.6/product-guides/dragen-v4.6/dragen-reference-support.md). # DRAGEN Reference Support DRAGEN supports the construction of reference hash tables for both human and non-human reference genomes. The reference autodetect feature of DRAGEN is able to recognize the reference hash tables build on the four Human reference genomes: hg19 (`hg19`), GRCh37/hs37d5 (`hs37d5`), GRCh38/hs38d1(`hg38`), and T2T-CHM13v2.0 (`chm13`). DRAGEN supports pangenome reference hash tables which extend the reference genomes with alternative variant paths from a sample cohort used to construct the pangenome reference. A pangenome-based reference improves the mapping accuracy of Illumina reads in the “Difficult-to-Map Regions” of the genome and the downstream variant calling. Pre-built human references are available for download at [DRAGEN Software Support Site page](https://support.illumina.com/sequencing/sequencing_software/dragen-bio-it-platform/product_files.html). The pangenome is the recommended reference for germline human analyses. The accuracy achieved with pangenome references are highlighted in the plot below. ![](https://400428970-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FS6tWlZO1JqcbWYgnhR2X%2Fuploads%2Fgit-blob-928cdaef8e9aec86d2ba185e44e0530881bcdd94%2Fpangenome_v_linear_accuracy.png?alt=media) Somatic pipelines support both linear and pangenome human references. Linear remains the reference type against which somatic accuracy has been characterized, but pangenome is fully supported and may be used. This is particularly useful for Tumor-Normal workflows where the Normal is (or was) processed through a germline pipeline on pangenome: aligning the tumor to the same pangenome reference removes the ambiguity introduced by mapping tumor and normal against different reference types, and allows the Tumor-Normal variant call to reuse the already-mapped Normal without remapping. It also lets labs that run both germline and somatic pipelines maintain a single shared hashtable. Users switching an existing somatic workflow from linear to pangenome should validate performance for their specific application. In the following tables we summarize the reference support for each DRAGEN component and the recommended reference type for each component. | Pipeline | hg19 | hs37d5 | hg38 | chm13 | non-human | Recommended (human) | Recommended (non-human) | | -------------------------- | --------- | --------- | ---- | --------- | --------- | ------------------- | ----------------------- | | **Germline** | Yes | Yes | Yes | *Note1\** | Yes | Pangenome | Linear | | **Somatic** | Yes | Yes | Yes | *Note2\** | No | Linear or Pangenome | Not supported | | **RNA** | Yes | Yes | Yes | *Note1\** | Yes | Linear | Linear | | **Methyl 5-base Germline** | Yes | Yes | Yes | No | No | Pangenome | Not supported | | **Methyl 5-base Somatic** | Yes | Yes | Yes | No | No | Linear or Pangenome | Not supported | | **Methyl TruSeq** | Yes | Yes | Yes | No | No | Linear | Not supported | | **scRNA** | Yes | Yes | Yes | *Note1\** | Yes | Linear | Linear | | **TruPath** | *Note3\** | *Note3\** | Yes | No | No | Pangenome | Not supported | | **Annotation** | Yes | Yes | Yes | No | Yes | Pangenome | Linear | *Note1\* DRAGEN™ supports the component execution; however, the component's accuracy has not been established. Validated only for SNV. Accuracy not validated for CNV, SV, Joint Genotyping, HLA, gVCFGenotyper, RNA and scRNA. Not supported for STR, Targeted Callers, MRJD* *Note2\* DRAGEN™ supports the component execution; however, the component's accuracy has not been established.* *Note3\* Experimental use only. The component's functionality and accuracy has not been established with this reference.* ### Component availability per pipeline | Pipeline | Components | | ----------- | ------------------------------------------------------------------------------------------------------------------- | | Germline | SNV, CNV, SV, STR\*, Targeted Callers\*, MRJD\*, RNA, De Novo, Joint Genotyping, Biomarkers (HLA)\*, gVCF genotyper | | Somatic | SNV, UMI SNV, CNV, SV | | Methylation | 5-base, TruSeq DNA Methyl, TruSeq Methyl Capture | | Single cell | RNA, ATAC | | TruPath | SNV, CNV, SV, STR, Targeted Callers, MRJD | | Annotation | Nirvana | \*Not supported with non-human reference. By default, DRAGEN will error out if a linear reference is provided when running a component for which a pangenome reference is required as listed in the above table. If you are sure that a linear reference is desired, the error can be suppressed by setting `--validate-pangenome-reference=false`. See [Prepare a Reference Genome](/dragen/dragen-v4.6/product-guides/dragen-v4.6/dragen-reference-support/prepare-a-reference-genome.md) for how to build a custom reference genome. See [hg19 Reference Configurations](/dragen/dragen-v4.6/product-guides/dragen-v4.6/dragen-reference-support/hg19-configurations.md) for recipes to build PAR-masked and rCRS variants of the hg19 reference. --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. 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