PRISM: Pair-read informed split-read mapping for base-pair level detection of insertion, deletion and structural variants

Motivation: The development of high-throughput sequencing technologies has enabled novel methods for detecting structural variants (SVs). Current methods are typically based on depth of coverage or pair-end mapping clusters. However, most of these only report an approximate location for each SV, rather than exact breakpoints. Results: We have developed pair-read informed split mapping (PRISM), a method that identifies SVs and their precise breakpoints from whole-genome resequencing data. PRISM uses a split-alignment approach informed by the mapping of paired-end reads hence enabling breakpoint identification ofmultiple SV types, including arbitrary-sized inversions, deletions and tandem duplications. Comparisons to previous datasets and simulation experiments illustrate PRISM's high sensitivity, while PCR validations of PRISM results including previously uncharacterized variants, indicate an overall precision of ∼90%.