GRIDSS2: harnessing the power of phasing and single breakends in somatic structural variant detection

Daniel L Cameron; Jonathor Baber; Charles Shale; Jose Espejo Valle-Inclan; Nicolle Besselink; Edwin Cuppen; Peter Priestley; Anthony T Papenfuss

doi:10.1101/2020.07.09.196527

bioRxiv · 10.1101/2020.07.09.196527

GRIDSS2: harnessing the power of phasing and single breakends in somatic structural variant detection

Daniel L Cameron·Jonathor Baber·Charles Shale·Jose Espejo Valle-Inclan·Nicolle Besselink·Edwin Cuppen·Peter Priestley·Anthony T Papenfuss

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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.

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Daniel L Cameron, Jonathor Baber, Charles Shale, Jose Espejo Valle-Inclan, Nicolle Besselink, Edwin Cuppen, Peter Priestley, Anthony T Papenfuss. 2020-07-10. GRIDSS2: harnessing the power of phasing and single breakends in somatic structural variant detection. https://doi.org/10.1101/2020.07.09.196527

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