Dikshant Pradhan and Mohammed El-Kebir. On the Non-uniqueness of Solutions to the Perfect Phylogeny Mixture Problem

Abstract: Tumors exhibit extensive intra-tumor heterogeneity, the presence of groups of cellular populations with distinct sets of somatic mutations. This heterogeneity is the result of an evolutionary process, which is described by a phylogenetic tree. The problem of reconstructing a phylogenetic tree T given bulk sequencing data from a tumor is more complicated than the classic phylogeny inference problem. That is, rather than observing the leaves of T directly, we are given mutation frequencies that are the result of mixtures of the leaves of T. The majority of current tumor phylogeny inference methods employ the perfect phylogeny evolutionary model.
In this work, we show that the underlying PERFECT PHYLOGENY MIXTURE combinatorial problem typically has multiple solutions.
We provide a polynomial-time computable upper bound on the number of solutions. We use simulations to identify factors that contribute to and counteract non-uniqueness of solutions. In addition, we study the sampling performance of current methods, identifying significant biases.

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