Supplementary Figure 3: Estimation of the percentage of blood cells affected by LOY through analysis of SNP array data from PAR1 of chromosomes X and Y using MAD software in the ULSAM cohort.

PAR1 is the largest of the PARs (regions with homologous sequences on chromosomes X and Y) with coordinates 10,001–2,649,520 on chromosome Y and 60,001–2,699,520 on chromosome X. MAD software is a tool for the detection and quantification of somatic structural variants from SNP array data, which uses diploid BAF values for the identification and LRR values for the quantification of somatic variants, and is not originally intended for analyses of chromosome Y data. However, by using the correlation between LRR in the PAR1 region of the Y chromosome and dBAF (absolute deviation from the expected BAF value of 0.5 in heterozygous probes) of the PAR1 region of chromosomes X and Y (panel a), we could use MAD quantification of the diploid PAR1 region on chromosomes X and Y to calculate the percentage of cells affected by LOY (panel b) in a two-step process. For example, the dBAF value at the LRR threshold for survival analyses (mLRR-Y ≤ –0.4) can be found using the equation given in panel a (0.178). This equation (y = –2.7823x + 0.0954) is describing the relationship between mLRR-Y on chromosome Y and dBAF on chromosomes X and Y for the 1,141 subjects. Next, the percentage of cells affected by LOY can be found by applying the equation in panel b that describes the relationship between dBAF and the percentage of cells as estimated by MAD software for 14 cases (y = 1.832x + 0.023). For this example, dBAF of 0.178 translates to LOY in 35% of cells.