HRD calculation
The HRD score is calculated as the weighted sum of three different chromosomal event types [Abkevich et al., 2012,Birkbak et al., 2012,de Luca et al., 2020]:
- Loss-of-heterozygosity (LOH).
- Large-scale state transition (LST).
- Telomeric allelic imbalance (TAI).
The weights are rescaled such that they sum to 3.
Loss-of-heterozygosity
Regions are considered LOH regions if they:
- Have a ploidy state corresponding to LOH (table 10.1), i.e. have copy numbers (0,1), (0,2), (0,3), or (0,4).
- Have a length equal to or larger than Minimum LOH length (Mb).
- Are located on a chromosome where not all regions correspond to LOH.
Large-scale state transition
Two adjacent regions lead to an LST event if they:
- Are located on the same chromosome arm.
- Each have a length equal to or larger than Minimum LST length (Mb).
- Are separated by a distance smaller than Maximum LST region distance (Mb).
Telomeric allelic imbalance
Regions are considered TAI regions if they:
- Extend to the telomeres. The region closest to the chromosome end is used as a proxy.
- Do not extend to the centromere.
- Show an allelic imbalance, which is defined as at least one of the following:
- Have a ploidy state corresponding to LOH (table 10.1).
- Have different minor and major copy numbers (table 10.1), and the most prevalent copy number of the chromosome is either even or 1.
- Have a total copy number (table 10.1) that differs from the most prevalent copy number of the chromosome.
The most prevalent copy number of the chromosome is calculated as the most frequent total copy number on the chromosome.