What are the challenges in detecting structural variants and what methods are used?

Structural variants (SVs: deletions, duplications, inversions, translocations >50bp) are challenging to detect due to complexity and size. Detection methods by evidence type: 1) Read-pair - discordant mapping (unexpected orientation/distance) indicates SVs; Delly, Lumpy. 2) Split-reads - alignments spanning breakpoints; Pindel. 3) Read-depth - copy number changes from coverage; CNVnator, cn.MOPS. 4) Assembly - local or de novo assembly resolves complex events; SvABA, GRIDSS. 5) Long-reads - span entire SVs enabling direct detection; Sniffles, PBSV, cuteSV; gold standard for complex regions. Challenges: repetitive regions, false positives at mapping artifacts, merging calls across methods, breakpoint resolution, haplotype phasing, genotyping. Best practice: combine methods, use SV callers with different evidence types, ensemble calling (SURVIVOR), validate with orthogonal methods.