GRIDSS2: comprehensive characterisation of somatic structural variation using single breakend variants and structural variant phasing

Abstract

GRIDSS2 is the first structural variant caller to explicitly report single breakends - breakpoints in which only one side can be unambiguously determined. By treating single breakends as a fundamental genomic rearrangement signal on par with breakpoints, GRIDSS2 can explain 47% of somatic centromeric copy number changes using single breakends to non-centromeric sequence, with chromosome 1 exhibiting a unique centromeric rearrangement signature. On a cohort of 3,782 deeply sequenced metastatic cancers, GRIDSS2 achieved an unprecedented 3.1% false negative rate and identified a novel 32-100bp duplication signature. Somatic structural variants are highly clustered with GRIDSS2 phasing 16% using just paired-end sequencing.