Additional file 5: of Exome sequencing of primary breast cancers with paired metastatic lesions reveals metastasis-enriched mutations in the A-kinase anchoring protein family (AKAPs)
Figures S3a and S3b. Estimation of LOH fraction and tumor content. Estimation of LOH fraction and tumor content using a Beta-Normal mixture model. Histograms show the distribution of major allele frequencies (range: 50–100%) and red curves show the mixture model estimated from the data. The set of SNPs called in the germline sample was considered in the tumor sample (primary and metastasis independently). When genomes contain regions of LOH, the distribution will be bimodal, as illustrated in the inset (top right). The first component (closer to 50%; red in inset) represents heterozygous SNPs in regions without LOH and was modeled as a normal distribution with a mean close to 50% in a perfect sample, but will increase towards 100% as allelic dropout increases. The second component (closer to 100%; blue in inset) represents homozygous SNPs in regions with LOH, was modeled as a beta distribution with two parameters (the mean of this component should be close to 100% and increase as LOH fraction increases and decrease as with non-cancer cell contamination. The mixture distribution thus had four free parameters plus the mixture proportion, the latter representing the estimated LOH fraction of the sample. Fitting this mixture to the observations yielded estimates for LOH fraction, tumor fraction and allelic dropout rate for each sample (Additional file 3: Figure S2). Model fitting was performed using the EstimatedDistribution function of Mathematica 9.0 (Wolfram Research Inc.). (ZIP 421 kb
