Constraints on the perfect phylogeny mixture model and their effect on reducing degeneracy

TL;DR

This paper investigates the limitations of the perfect phylogeny mixture model in resolving evolutionary tree ambiguity and introduces new constraints to reduce degeneracy, supported by theoretical analysis over large problem ensembles.

Contribution

It demonstrates the ineffectiveness of existing longitudinal constraints and proposes novel constraints that better limit solution ambiguity in the PPM model.

Findings

Longitudinal constraints often fail to reduce tree ambiguity.

New constraints can significantly decrease the number of plausible phylogenetic trees.

Theoretical results hold across large ensembles of inference problems.

Abstract

The perfect phylogeny mixture (PPM) model is useful due to its simplicity and applicability in scenarios where mutations can be assumed to accumulate monotonically over time. It is the underlying model in many tools that have been used, for example, to infer phylogenetic trees for tumor evolution and reconstruction. Unfortunately, the PPM model gives rise to substantial ambiguity -- in that many different phylogenetic trees can explain the same observed data -- even in the idealized setting where data are observed perfectly, i.e. fully and without noise. This ambiguity has been studied in this perfect setting by Pradhan et al. 2018, which proposed a procedure to bound the number of solutions given a fixed instance of observation data. Beyond this, studies have been primarily empirical. Recent work (Myers et al. 2019) proposed adding extra constraints to the PPM model to tackle ambiguity. In this paper, we first show that the extra constraints of Myers et al. 2019, called longitudinal constraints (LC), often fail to reduce the number of distinct trees that explain the observations. We then propose novel alternative constraints to limit solution ambiguity and study their impact when the data are observed perfectly. Unlike the analysis in Pradhan et al. 2018, our theoretical results regarding both the inefficacy of the LC and the extent to which our new constrains reduce ambiguity are not tied to a single observation instance. Rather, our theorems hold over large ensembles of possible inference problems. To the best of our knowledge, we are the first to study degeneracy in the PPM model in this ensemble-based theoretical framework.