# 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 for Germline human analyses. The accuracy achieved with pangenome references are highlighted in the plot below.

![](https://3660538983-files.gitbook.io/~/files/v0/b/gitbook-x-prod.appspot.com/o/spaces%2FpFn0gLe5V859SXejQNAW%2Fuploads%2Fgit-blob-daf64b84d6ea5298bdd158ccfcd5b3e661b772e9%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.

### Germline

| Component        | Recommended Human Reference Type | Recommended Non-Human Reference Type | Human hg19 | Human hs37d5 | Human hg38 | Human chm13 | Non-Human |
| ---------------- | :------------------------------: | :----------------------------------: | :--------: | :----------: | :--------: | :---------: | :-------: |
| SNV              |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |     Yes     |    Yes    |
| CNV              |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |     No    |
| SV               |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |    Yes    |
| Expansion Hunter |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |      No     |     No    |
| Targeted Callers |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |      No     |     No    |
| RNA              |              Linear              |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |    Yes    |
| De Novo          |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |    Yes    |
| Joint Genotyping |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |    Yes    |
| Biomarkers (HLA) |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |     No    |
| gVCF genotyper   |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |    Yes    |

### Somatic

| Component | Recommended Human Reference Type | Recommended Non-Human Reference Type | Human hg19 | Human hs37d5 | Human hg38 | Human chm13 | Non-Human |
| --------- | :------------------------------: | :----------------------------------: | :--------: | :----------: | :--------: | :---------: | :-------: |
| SNV       |              Linear              |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |     No    |
| UMI SNV   |              Linear              |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |     No    |
| CNV       |              Linear              |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |     No    |
| SV        |              Linear              |                Linear                |     Yes    |      Yes     |     Yes    |    Yes\*    |     No    |

### Methylation

| Component   | Recommended Human Reference Type | Recommended Non-Human Reference Type | Human hg19 | Human hs37d5 | Human hg38 | Human chm13 | Non-Human |
| ----------- | :------------------------------: | :----------------------------------: | :--------: | :----------: | :--------: | :---------: | :-------: |
| Methylation |              Linear              |                Linear                |     Yes    |      Yes     |     Yes    |      No     |     No    |

### Annotation

| Component | Recommended Human Reference Type | Recommended Non-Human Reference Type | Human hg19 | Human hs37d5 | Human hg38 | Human chm13 | Non-Human |
| --------- | :------------------------------: | :----------------------------------: | :--------: | :----------: | :--------: | :---------: | :-------: |
| Nirvana   |             Pangenome            |                Linear                |     Yes    |      Yes     |     Yes    |      No     |    Yes    |

\* DRAGEN supports the component execution, however the component's accuracy has not been established.

See [Prepare a Reference Genome](https://help.connected.illumina.com/dragen/dragen-v4.3/product-guide/dragen-v4.3/dragen-reference-support/prepare-a-reference-genome) for how to build a custom reference genome.