Moncunill, V. et al. Nat. Biotechnol. doi:10.1038/nbt.3027 (26 October 2014).

Tumor genomes can have high structural variation caused by, for example, deletions, insertions and translocations. Detecting these variants in sequence data is challenging, and most tools specialize in finding certain mutation classes. Moncunill et al. take an unusual approach in their somatic mutation finder (SMUFIN), which compares tumor and matched normal genomic sequence reads directly and uses a tree structure to identify tumor-specific reads that are likely to bear mutations. Tumor reads are then grouped into blocks and processed by mutation type. SMUFIN can uncover single-base changes as well as structural variation of any size at base-pair resolution and does not rely on sequence alignment to a reference genome, making it fast. The researchers used SMUFIN to detect changes in blood and solid tumors, including highly complex variation indicative of chromothripsis.