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

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 for how to build a custom reference genome.