Gustaf: Detecting and correctly classifying SVs in the NGS twilight zone

• DOI: 10.1093/bioinformatics/btu431
• Publication Date: 2014-07-16T00:23:13Z
• Authors: Kathrin Trappe; Anne-Katrin Emde; Hans-Christian Eh...; Knut Reinert
• Keywords: 0301 basic medicine; 03 medical and health sciences; Genomic Structural Variation; High-Throughput Nucleotide Sequencing; Humans; Sequence Analysis, DNA; Sequence Alignment; Software; Translocation, Genetic; Sequence Deletion

Abstract Motivation: The landscape of structural variation (SV) including complex duplication and translocation patterns is far from resolved. SV detection tools usually exhibit low agreement, are often geared toward certain types or size ranges of variation and struggle to correctly classify the type and exact size of SVs. Results: We present Gustaf (Generic mUlti-SpliT Alignment Finder), a sound generic multi-split SV detection tool that detects and classifies deletions, inversions, dispersed duplications and translocations of ≥30 bp. Our approach is based on a generic multi-split alignment strategy that can identify SV breakpoints with base pair resolution. We show that Gustaf correctly identifies SVs, especially in the range from 30 to 100 bp, which we call the next-generation sequencing (NGS) twilight zone of SVs, as well as larger SVs >500 bp. Gustaf performs better than similar tools in our benchmark and is furthermore able to correctly identify size and location of dispersed duplications and translocations, which otherwise might be wrongly classified, for example, as large deletions. Availability and implementation: Project information, paper benchmark and source code are available via http://www.seqan.de/projects/gustaf/ . Contact: [e-mail]