Accurately Estimating Tumor Purity of Samples with High Degree of Heterogeneity from Cancer Sequencing Data

Tumor purity is the proportion of tumor cells in the sampled admixture. Estimating tumor purity is one of the key steps for both understanding the tumor micro-environment and reducing false positives and false negatives in the genomic analysis. However, existing approaches often lose some accuracy when analyzing the samples with high degree of heterogeneity. The patterns of clonal architecture shown in sequencing data interfere with the data signals that the purity estimation algorithms expect. In this article, we propose a computational method, EMPurity, which is able to accurately infer the tumor purity of the samples with high degree of heterogeneity. EMPurity captures the patterns of both the tumor purity and clonal structure by a probabilistic model. The model parameters are directly calculated from aligned reads, which prevents the errors transferring from the variant calling results. We test EMPurity on a series of datasets comparing to three popular approaches, and EMPurity outperforms them on different simulation configurations.