WGS Small Variants

Generated on 2026-05-07

Small variants

The DRAGEN Germline Small Variant Caller takes mapped and aligned DNA reads as input and calls SNPs and indels through a combination of column-wise detection and local de novo assembly of haplotypes. For more information, refer to the DRAGEN user guide.

DRAGEN: DRAGEN 4.4.6 vs 4.5.4 | Truthset: GIAB/NIST high-confidence, GIAB/NIST v4.2.1 | Reference: GRCh38

Results reported for HG001-HG007 sequenced with NSX 1.3 with 10B flow cell downsampled at 35x raw coverage.

SNPs table (click to expand)

Sample	Version	Recall	Precision	F1-score	FN	FP
HG001	4.4.6	1.000	0.999	0.999	1336	2634
HG001	4.5.4	1.000	1.000	1.000	721	1658
HG002	4.4.6	0.999	1.000	0.999	2896	1749
HG002	4.5.4	0.999	1.000	1.000	2198	1026
HG003	4.4.6	0.999	0.999	0.999	3511	3005
HG003	4.5.4	0.999	0.999	0.999	2936	2338
HG004	4.4.6	0.999	0.999	0.999	3748	2584
HG004	4.5.4	0.999	1.000	0.999	2963	1803
HG005	4.4.6	0.999	0.999	0.999	3023	2047
HG005	4.5.4	0.999	1.000	0.999	2413	1369
HG006	4.4.6	0.999	0.999	0.999	3103	2408
HG006	4.5.4	0.999	1.000	0.999	2484	1699
HG007	4.4.6	0.999	0.999	0.999	3467	2327
HG007	4.5.4	0.999	1.000	0.999	2955	1602

Indels table (click to expand)

Sample	Version	Recall	Precision	F1-score	FN	FP
HG001	4.4.6	0.996	0.997	0.997	1867	1437
HG001	4.5.4	0.996	0.997	0.997	1849	1231
HG002	4.4.6	0.996	0.997	0.997	2101	1421
HG002	4.5.4	0.996	0.998	0.997	1998	1229
HG003	4.4.6	0.996	0.997	0.997	1852	1420
HG003	4.5.4	0.997	0.998	0.997	1789	1164
HG004	4.4.6	0.996	0.997	0.997	1898	1384
HG004	4.5.4	0.996	0.998	0.997	1877	1226
HG005	4.4.6	0.998	0.998	0.998	897	670
HG005	4.5.4	0.998	0.999	0.998	810	554
HG006	4.4.6	0.997	0.998	0.998	1147	838
HG006	4.5.4	0.997	0.998	0.998	1116	741
HG007	4.4.6	0.997	0.998	0.998	1246	868
HG007	4.5.4	0.997	0.998	0.998	1161	762

HG001-HG007, NSX 10B v1.3, 35x raw coverage

HG002 T2TQ100 performance

DRAGEN: 4.4.6 vs 4.5.4 | Truthset: T2TQ100-v1.1-v0.019 | Reference: GRCh38

HG002 T2TQ100-v1.1-v0.019 small variants comparison (click to expand)

Version	SNPs FN	SNPs FP	SNPs FP+FN	Indels FN	Indels FP	Indels FP+FN
4.4.6	21571	8752	30323	40208	23681	63889
4.5.4	16490	5764	22254	36945	19661	56606

HG002 T2TQ100-v1.1-v0.019 FP+FN comparison

A legacy of continuous innovation and improving accuracy in each version.

Historical HG002 benchmarked releases using the HG002 small variants NIST v4.2.1 truthset show FP+FN dropping from 41,244 in DRAGEN 3.4.5 to 4,364 in DRAGEN 4.5.4.

Historical version trend table (click to expand)

Version	FP+FN
3.4.5	41,244
3.5.7	40,056
3.6.3	39,046
3.7.5	21,479
3.8.4	20,402
3.9.3	19,052
3.10.4	12,851
4.0.3	12,815
4.2.4	11,163
4.3.3	6,615
4.4.6	5,955
4.5.4	4,364

WGS small variants FP+FN improvement across DRAGEN versions

Mosaic detection

Non-cancer post-zygotic mosaic variants have typical allele fraction (AFs) lower than 50% and therefore more challenging to find with the default small variant caller that has been optimized to detect germline variants with typical AFs of 0%, 50% or 100%. The Mosaic variant caller has been designed to address this gap by training a dedicated machine learning model trained on lowAF variants. For more information, refer to the DRAGEN user guide.

DRAGEN: DRAGEN 4.5.4 vs 4.4.6 | Truthset: HG002 NIST Mosaic v1.0 | Reference: GRCh38 Results reported for HG002 sample fastqs sequenced with HiSeq2500 at 300x available from NIST.

HG002 mosaic small variants comparison (click to expand)

Version	SNPs FN	SNPs FP	SNPs TP	SNPs FP+FN	Indels FN	Indels FP	Indels TP	Indels FP+FN
4.4.6	0	318	85	318	0	196	0	196
4.5.4	0	311	85	311	0	185	0	185

HG002 Mosaic FP comparison