Indelsignaturen

Indelsignaturen, or indel mutational signatures, denote characteristic patterns of somatic insertions and deletions observed in the genome, especially in cancers. They complement single-base substitution signatures in describing mutational processes active in a tumor or tissue.

They are typically described by mutation type (insertion vs deletion), size category (1–2 bp, 3–10 bp, greater than 10 bp), and the sequence context at the breakpoint (for example, whether deletions occur in repetitive regions or show microhomology at the ends). Such features capture processes including replication errors, repair pathway choice, and exposure to mutagens.

Indel signatures are inferred from large-scale sequencing data using deconvolution methods such as non-negative matrix factorization. The input is a catalog of somatic indels across many samples; the method estimates a set of signatures and the exposure of each sample to those signatures. The interpretation links signatures to biology: mismatch repair deficiency often yields many small indels in microsatellite regions; microhomology at deletion junctions points to microhomology-mediated end joining; deletions with microduplication patterns can reflect replication stress or BRCA-related repair defects.

Applications include cancer classification, prognosis, and guiding therapy by signaling specific DNA repair defects. Indel signatures are typically reported alongside other mutational signatures and are integrated with SBS (single-base substitution) profiles to give a comprehensive view of mutational processes.

Limitations include biases in indel calling, sequencing technology effects, and the need for sufficient sample sizes to robustly identify signatures.