Tumor Phylogeny Topology Inference via Deep Learning

Abstract

SummaryPrincipled computational approaches for tumor phylogeny reconstruction via single-cell sequencing typically aim to build the most likely perfect phylogeny tree from the noisy genotype matrix - which represents genotype calls of single-cells. This problem is NP-hard, and as a result, existing approaches aim to solve relatively small instances of it through combinatorial optimization techniques or Bayesian inference. As expected, even when the goal is to infer basic topological features of the tumor phylogeny - rather than reconstructing the topology entirely, these approaches could be prohibitively slow. In this paper, we introduce fast deep-learning solutions to the problems of inferring whether the most likely tree has a linear (chain) or branching topology and whether a perfect phylogeny is feasible from a given genotype matrix. We also present a reinforcement learning approach for reconstructing the most likely tumor phylogeny. This preliminary work demonstrates that data-driven approaches can reconstruct key features of tumor evolution.