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.

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

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.

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 for how to build a custom reference genome.