Mosaic Detection
The default mode of the small variant caller has been optimized to detect germline variants with typical AFs of 0%, 50% or 100%. Non-cancer post-zygotic mosaic variants have typical allele frequencies (AFs) lower than 50% and therefore more challenging to find with the default small variant caller. To improve sensitivity of low AF calls, a new machine learning (ML) model trained using read and context evidence from low AF calls is used. This allows the model to identify variants down to approximately 5% AF on 35x WGS and 3% AF on 300x WGS. The mosaic ML model is applied to all calls that are rejected by the germline model and variants detected with the mosaic detection are identified by a MOSAIC
flag in the VCF INFO field.

MOSAIC
tagged variants with QUAL
smaller than 3.0103
are filtered with the MosaicHardQUAL
filter.
We provide an optional MosaicLowAF
filtering option to filter MOSAIC
tagged variants with AF
smaller than the AF
threshold. The threshold for this filter can be set with the --vc-mosaic-af-filter-threshold
option. The default value for the mosaic AF
filter threshold is set to 0.2
if the median depth of the sample detected by the ploidy caller is <= 100x
and 0.1
if the detected depth is >100x
. All MOSAIC
variants can be reported, regardless of their AF
, with the --vc-mosaic-af-filter-threshold=0
option. For haploid regions, we apply separate handling that uses a threshold of 0.75
for assigning MOSAIC
tags. Please refer to the Ploidy Support section for more details.
Furthermore, the output of MOSAIC
tagged calls can be restricted using an optional target BED provided with the --vc-mosaic-target-bed
option.
Command line options
--vc-enable-mosaic-detection
Set to true to enable mosaic detection. Set to false to disable mosaic detection.
--vc-mosaic-af-filter-threshold
Set the allele frequency threshold for the application of the
MosaicLowAF
filter to mosaic calls. AllMOSAIC
tagged variants withAF
smaller than theAF
threshold are filtered with theMosaicLowAF
filter. The default mosaicAF
filter threshold is set to0.2
if the median depth of the sample detected by the ploidy caller is<= 100x
and0.1
if the detected depth is> 100x
.--vc-mosaic-qual-filter-threshold
Set the
QUAL
threshold for the application of theMosaicHardQUAL
filter to mosaic calls. AllMOSAIC
tagged variants withQUAL
smaller than the thresholdQUAL
are filtered with theMosaicHardQUAL
filter. The default mosaicQUAL
filter threshold is set to3.0103
.--vc-mosaic-target-bed
Optional target BED file to restrict the output of
MOSAIC
tagged variant calls only in the specified regions.
Comparison with DRAGEN 4.2 High Sensitivity Mode and DRAGEN v4.3 Mosaic
Small variant calling features comparison between default germline small variant caller and mosaic detection mode in DRAGEN 4.2, DRAGEN 4.3 and DRAGEN 4.4
4.2
DRAGEN 4.2 default Small Variant Caller
--enable-variant-caller=true
3
No
No
N/A
4.2 HSM
DRAGEN 4.2 High Sensitivity Mode
--enable-variant-caller=true --vc-enable-high-sensitivity-mode=true
0.4
Yes
Yes (Alpha)
N/A
4.3
DRAGEN 4.3 default Small Variant Caller
--enable-variant-caller=true
3
Yes
Yes (Full)
20%
4.3 Mosaic
DRAGEN 4.3 Mosaic Detection Mode
--enable-variant-caller=true --vc-enable-mosaic-detection=true
0.4
Yes
Yes (Full)
0%
4.4
DRAGEN 4.4 default Small Variant Caller
--enable-variant-caller=true
3.0103
Yes
Yes (Full)
20% if depth <=100x, 10% otherwise
4.4
DRAGEN 4.4 default Small Variant Caller
--enable-variant-caller=true --vc-enable-mosaic-detection=true
3.0103
Yes
Yes (Full)
20% if depth <=100x, 10% otherwise
4.4 Mosaic
DRAGEN 4.4 Mosaic Detection Mode
--enable-variant-caller=true --vc-enable-mosaic-detection=true --vc-mosaic-af-filter-threshold=0
3.0103
Yes
Yes (Full)
0%
Comparison with DRAGEN 4.3 command line behavior
The command line behavior of --vc-enable-mosaic-detection=true
has changed between DRAGEN 4.3 and DRAGEN 4.4. In DRAGEN 4.3, explicitly setting --vc-enable-mosaic-detection=true
caused two changes to default behavior:
The hard filter
QUAL
threshold for both SNPs and INDELs is lowered to0.4
in this mode to allow low AF calls to be set asPASS
in the FILTER field.The mosaic
AF
filter threshold is set to0.0
.
In DRAGEN 4.4, to improve the user experience, both these changes have been decoupled from the --vc-enable-mosaic-detection=true
option, therefore the user can report all MOSAIC
variants, regardless of their AF
, with the --vc-mosaic-af-filter-threshold=0
option.
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