Here we propose novel algorithms to characterize large (>40 Kbp) interspersed segmental duplications, (> 80 Kbp) inversions, (> 100 Kbp) deletions, and (> 100 Kbp) translocations using Linked-Read sequencing data. Linked-Read sequencing provides long range information, where Illumina reads are tagged with barcodes that can be used to assign short reads to pools of larger (30-50 Kbp) molecules. Our methods rely on split molecule sequence signature that we have previously described. Similar to the split read, split molecules refer to large segments of DNA that span an SV breakpoint. Therefore, when mapped to the reference genome, the mapping of these segments would be discontinuous. We redesign our earlier algorithm, VALOR, to specifically leverage Linked-Read sequencing data to discover large structural variation. We implement our new algorithms in a new software package, called VALOR2.

Illumina simulation CRAM files. Aligned to GRCh37 using BWA - Part 1