Variant calling

After reads are aligned to a reference genome, a variant caller decides at each position whether an apparent difference is a real mutation or a sequencing artifact. Somatic callers compare tumor against matched normal to keep only tumor-specific (somatic) variants.

Accuracy here directly caps the value of everything downstream: false positives inject phantom neoantigens that waste vaccine slots, false negatives drop real targets entirely, and quality degrades in low-purity samples. Because the whole target list is gated at this step, it's an underappreciated place where a better pipeline can quietly outperform.