TakeABreak

TakeABreak is a prototype, reference-free structural variant caller designed to detect genomic inversion breakpoints directly from raw short-read NGS data without requiring either read mapping to a reference genome or full de novo assembly. It is based on a formal model showing that inversions induce a fixed-size, characteristic topological pattern in the de Bruijn graph built from sequencing reads. TakeABreak searches the assembly graph for these inversion-specific signatures and reports candidate breakpoints.

The method explicitly analyzes sources of false positives and false negatives arising from graph complexity (e.g., repeats and sequencing artifacts) and couples the graph-topology detector with a sequence-based filtering step that improves the precision–recall trade-off. In evaluations on simulated inversions spanning genomes of increasing complexity (from E. coli to a human-chromosome–scale dataset), TakeABreak achieved promising accuracy with low memory requirements and modest computational runtime, supporting targeted detection of balanced structural variants in settings where a high-quality reference genome is unavailable or unsuitable.