Mutational Signatures (v3.5 - November 2025)

The scheme corresponds to three heterozygosity states:

1. heterozygous segments with copy number of [A>0, B>0] (numbers reflect the counts for major allele A and minor allele B)
2. segments with LOH with copy number of [A>0, B=0]
3. segments with homozygous deletions [A=0, B=0]

Segments are further subclassified into 6 classes based on the sum of major and minor allele (total copy number) and chosen for biological relevance:

1. total copy number (TCN)=0 (homozygous deletion)
2. TCN=1 (deletion leading to LOH)
3. TCN=2 (wild type, including copy-neutral LOH)
4. TCN=3 or 4 (minor gain)
5. TCN=5 to 8 (moderate gain)
6. TCN>=9 (high-level amplification).

Each of the heterozygous and LOH total copy number states are then organised into five classes based on the size of their segments: 0 – 100kb, 100kb – 1Mb, 1Mb – 10Mb, 10Mb – 40Mb, and >40Mb (the largest category for homozygous deletions was restricted to >1Mb) in order to capture focal, large scale, and chromosomal-scale copy number changes. This gives a total of 48 copy number context to categorise segments into (3x homozygous deletion categories, 5*5=25x LOH categories, 4*5=20 heterozygous categories).