DELLY is an integrated method for the discovery of genomic structural variants (SVs) at single-nucleotide resolution. It combines short-range and long-range paired-end mapping with split-read analysis to accurately identify various types of SVs, including deletions, tandem duplications, inversions, and translocations. The method is designed to handle different sequencing parameters, such as read length and insert size, and has been benchmarked on simulated data and real-world datasets from the 1000 Genomes Project and cancer genomes. DELLY demonstrates high sensitivity and specificity, with favorable performance compared to other SV prediction methods. The availability of DELLY and its application in various genomic studies highlight its utility in characterizing naturally occurring variation and understanding pathological somatic rearrangements.DELLY is an integrated method for the discovery of genomic structural variants (SVs) at single-nucleotide resolution. It combines short-range and long-range paired-end mapping with split-read analysis to accurately identify various types of SVs, including deletions, tandem duplications, inversions, and translocations. The method is designed to handle different sequencing parameters, such as read length and insert size, and has been benchmarked on simulated data and real-world datasets from the 1000 Genomes Project and cancer genomes. DELLY demonstrates high sensitivity and specificity, with favorable performance compared to other SV prediction methods. The availability of DELLY and its application in various genomic studies highlight its utility in characterizing naturally occurring variation and understanding pathological somatic rearrangements.