Figure 1

Simulated binary mixtures of aberrant and normal states. Mixtures of aberrant and normal states are reflected in deviations from the balance between A and B alleles in heterozygous SNPs and can be detected by simple measures. In panels A and B we display simulations of log R-ratio (ρ) and B allele frequency (β) spanning 1000 loci for mixtures of a normal state with a copy number of 2 with an aberrant state derived from this normal state with a copy number of 3 or 1. As the fraction of aberrant cells increases, the central band of the B-allele frequency, which exhibits the balance between A and B alleles, deviates to the outer band, indicating the dominance of one of the two alleles. The M-measure shown in panels C and D is a detector of allelic imbalance corresponding to the simulations shown in panels A and B, respectively. A limitation of the M-measure is that deviations of the M-measure from 0 for pure deletion states are indistinguishable from deviations in pure stromal states. This can be easily overcome by testing whether the log R-ratio is significantly below its expected value of 0. The combination of the log R-ratio and the M-measure indicates whether the aberrant state is a deletion (log R-ratio < 0) or duplication (log R-ratio > 0).