Structural Variant De Novo Quality Scoring

De novo quality scoring can be enabled for structural variant joint diploid calling, by setting --sv-denovo-scoring to true and supplying a pedigree file. This adds FORMAT/DQand FORMAT/DN fields to the output VCF file to represent a De Novo Quality Score and an associated De Novo call.

The following example shows a command line for enabling the de novo quality scoring for a joint diploid run.

dragen -f
--ref-dir <HASH_TABLE> \
--bam-input <BAM1> \
--bam-input <BAM2> \
--bam-input <BAM3> \
--enable-map align=false \
--enable-sv=true \
--output-directory <OUT_DIR> \
--output-file-prefix <PREFIX> \
--sv-denovo-scoring true \
--RGID DRAGEN_RGID \
--RGSM <sample name>
--pedigree-file <PED_FILE>

Consumable Prefix can also be run on an existing Structural Variant output VCF containing multiple samples (ie, a Trio with a Proband and Parents) to generate a modified VCF file that contains FORMAT/DQ and FORMAT/DN fields (the original file is not changed).

The following example shows a command line for deriving the de novo quality score from an existing SV trio.

dragen -f \
--variant <TRIO_VCF_FILE> \
--pedigree-file <PED_FILE> \
--enable-map-align false \
--sv-denovo-scoring true \
--output-directory <OUT_DIR> \
--output-file-prefix <PREFIX>

The DQ field is defined as follows:

##FORMAT=<ID=DQ,Number=1,Type=Float,Description="Denovo quality">

The DQ field represents a score of the posterior probability of the variant being denovo in the proband. If it can be calculated, the score in Phred scale is added to the proband, while the other samples are marked with a period ( . ) to indicate missing.

For example, DQ scores of 13 and 20 would correspond to a posterior probability of a de novo variant of 0.95 and 0.99, respectively.

The DN Field is defines as follows:

##FORMAT=<ID=DN,Number=1,Type=String,Description="Possible values are 'DeNovo' or 'LowDQ'. Threshold for a passing de novo call is DQ >= 20">

DRAGEN compares valid (> 0) DQ scores with a threshold with default score of 20. A score greater than or equal to the threshold results in DN field of the sample set to DeNovo, while a score below the threshold is declared to be LowDQ. If there is not a valid DQ score (ie, DQ equals “0” or “.”,) the DN field is set to “.”

The threshold can be changed by using the --sv-denovo-threshold command line option. For example, if the threshold needs to be reduced to 10, add --sv-denovo-threshold 10 to the DRAGEN command line.

The inputs to this function are the VCF file and the Pedigree file that specifies which sample in the trio is the proband, mother, or father. In the scenario where there are multiple trios specified in the pedigree file (eg, multi-generation pedigree), DRAGEN automatically detects the trios and assesses the DeNovo variants on the proband sample of each trio.