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 reference 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.

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 for how to build a custom reference genome.