High Sensitivity Mode

The default mode of the DRAGEN small variant caller has been optimized to produce the lowest FP+FN count and to maximize the f-measure score for both SNPs and INDELs. For use cases where it is important to have lower FN calls, even at the expense of extra FP calls, a high sensitivity mode is available. There are two main changes when high sensitivity mode is enabled:

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Detection of variants in regions where all reads have MAPQ=0 Unlike in default mode, when high sensitivity mode is enabled, regions that only have MAPQ=0 reads are processed in the same way as other regions to call variants. Since the read alignments in these regions are ambiguous and to allow quick identification of such calls, the variants are tagged with INFO/EVENTTYPE=VARIANT_IN_HOMOLOGY_REGION.

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Detection of low AF calls The default DRAGEN ML model has been trained to identify germline calls with typical AFs of 0%, 50% or 100%. To improve sensitivity of low AF calls, a new ML model trained using read and context evidence from both germline and low AF calls is used. This allows the model to identify variants down to approximately 5% AF. The hard filter QUAL threshold for both SNPs and INDELs is lowered to 0.4 in this mode to allow low AF calls to be set as PASS in the FILTER field.