# 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.

![](/files/joUEGjcClWuJaO8need0)

In the following tables we summarize the reference support for each DRAGEN component and the recommended reference type for each component.

### Germline

#### Recommended reference type per component

| Component        | Human     | Non-Human |
| ---------------- | --------- | --------- |
| SNV              | Pangenome | Linear    |
| CNV              | Pangenome | Linear    |
| SV               | Pangenome | Linear    |
| Expansion Hunter | Pangenome | Linear    |
| Targeted Callers | Pangenome | Linear    |
| RNA              | Linear    | Linear    |
| De Novo          | Pangenome | Linear    |
| Joint Genotyping | Pangenome | Linear    |
| Biomarkers (HLA) | Pangenome | Linear    |
| gVCF genotyper   | Pangenome | Linear    |

#### Reference support

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

### Somatic

#### Recommended reference type per component

| Component | Human  | Non-Human |
| --------- | ------ | --------- |
| SNV       | Linear | Linear    |
| UMI SNV   | Linear | Linear    |
| CNV       | Linear | Linear    |
| SV        | Linear | Linear    |

#### Reference support

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

### Methylation

#### Recommended reference type per component

| Sample Prep           | Pipeline    | Human     | Non-Human |
| --------------------- | ----------- | --------- | --------- |
| 5-base                | Germline    | Pangenome | Linear    |
| 5-base                | Somatic     | Linear    | Linear    |
| TruSeq DNA Methyl     | Methylation | Linear    | Linear    |
| TruSeq Methyl Capture | Methylation | Linear    | Linear    |

#### Reference support

| Sample Prep           |   Pipeline  | Human hg19 | Human hs37d5 | Human hg38 | Human chm13 | Non-Human |
| --------------------- | :---------: | :--------: | :----------: | :--------: | :---------: | :-------: |
| 5-base Germline       |   Germline  |     Yes    |      Yes     |     Yes    |      No     |     No    |
| 5-base Somatic        |   Somatic   |     Yes    |      Yes     |     Yes    |      No     |     No    |
| TruSeq DNA Methyl     | Methylation |     Yes    |      Yes     |     Yes    |      No     |     No    |
| TruSeq Methyl Capture | Methylation |     Yes    |      Yes     |     Yes    |      No     |     No    |

### Annotation

#### Recommended reference type per component

| Species | Human     | Non-Human |
| ------- | --------- | --------- |
| Nirvana | Pangenome | Linear    |

#### Component support

| Component | Human hg19 | Human hs37d5 | Human hg38 | Human chm13 | Non-Human |
| --------- | :--------: | :----------: | :--------: | :---------: | :-------: |
| Nirvana   |     Yes    |      Yes     |     Yes    |      No     |    Yes    |

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

By default, DRAGEN will error out if a linear reference is provided when running a component for which a pangemome reference is recommended as listed in the above table. If the user is sure that a linear reference is reference is desired, the error can be suppressed by setting `--validate-pangenome-reference=false`.

See [Prepare a Reference Genome](/dragen-v4.4/product-guide/dragen-v4.4/dragen-reference-support/prepare-a-reference-genome.md) for how to build a custom reference genome.


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