A Bayesian Nonparametric Model for Reconstructing Tumor Subclones Based on Mutation Pairs

We present a feature allocation model to reconstruct tumor subclones based on mutation pairs. The key innovation lies in the use of a pair of proximal single nucleotide variants (SNVs) for the subclone reconstruction as opposed to a single SNV. Using the categorical extension of the Indian buffet process (cIBP) we define the subclones as a vector of categorical matrices corresponding to a set of mutation pairs. Through Bayesian inference we report posterior probabilities of the number, genotypes and population frequencies of subclones in one or more tumor sample. We demonstrate the proposed methods using simulated and real-world data. A free software package is available at http://www.compgenome.org/pairclone.