Mutstats: an Ultra-fast Computational Method to Determine Clonal Status of Somatic Mutations

Tumor cell population is a mixture of heterogeneous cell subpopulations, known as subclones.Identification of clonal status of mutations, i.e., whether a mutation occurs in all tumor cells or in a subset of tumor cells, is crucial for understanding tumor progression and developing personalized treatment strategies.We make three major contributions in this paper: (1) we summarize terminologies in the literature based on a unified mathematical representation of subclones;(2) we develop a simulation algorithm to generate hypothetical sequencing data that are akin to real data; and (3) we present an ultra-fast computational method, Mutstats, to infer clonal status of somatic mutations from sequencing data of tumors.The inference is based on a Gaussian mixture model for mutation multiplicities.To validate Mutstats, we evaluate its performance on simulated datasets as well as two breast carcinoma samples from The Cancer Genome Atlas project.