Accurate calibration of both the SCNA-fit and karyotype models to the true level of certainty implied by the data would allow for assignment of probabilities to each candidate solution; we do not believe that the models we have presented here sufficiently capture the complexity of cancer genomes to allow for such interpretations. Even with manual review, analysis with ABSOLUTE may occasionally result in incorrect interpretations, for example genome-doubling without subsequent detectable gains or losses would result in a solution implying half the true ploidy value, which in some cases may correspond to a plausible karyotype model. Alternately, when multiple subclonal SCNAs appear close to the midpoints between adjacent clonal peaks, a solution implying twice the true ploidy may be chosen. We note that samples with no reliably detected SCNAs could not be called in our framework (ploidy 2N or 4N; purity undetermined). Such samples were therefore excluded from downstream analysis (see below). Estimation of inference error-rate requires independent measurement of sample ploidy. Further validation experiments in diverse tumor types will help to clarify any disease specific caveats.
