# 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://25033470-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FG9szlFZupV6Q2DasL98y%2Fuploads%2Fgit-blob-928cdaef8e9aec86d2ba185e44e0530881bcdd94%2Fpangenome_v_linear_accuracy.png?alt=media)

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     | Recommended (Human) | Recommended (Non-Human) |
| ----------------- | --------- | --------- | ---- | --------- | ------------------- | ----------------------- |
| **Germline**      | Yes       | Yes       | Yes  | *Note1\** | Pangenome           | Linear                  |
| **Somatic**       | Yes       | Yes       | Yes  | *Note2\** | Linear              | Linear                  |
| **RNA**           | Yes       | Yes       | Yes  | *Note1\** | Linear              | Linear                  |
| **Methyl 5-base** | Yes       | Yes       | Yes  | No        | Pangenome           | Linear                  |
| **Methyl TruSeq** | Yes       | Yes       | Yes  | No        | Linear              | Linear                  |
| **scRNA**         | Yes       | Yes       | Yes  | *Note1\** | Linear              | Linear                  |
| **TruPath**       | *Note3\** | *Note3\** | Yes  | No        | Pangenome           | Linear                  |
| **Annotation**    | Yes       | Yes       | Yes  | No        | 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                                                                                                     |

By default, DRAGEN will error out if a linear reference is provided when running a component for which a pangenome reference is recommended 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](https://help.dragen.illumina.com/product-guides/dragen-v4.5/dragen-reference-support/prepare-a-reference-genome) for how to build a custom reference genome.