Determining distances and consensus between mutation trees

TL;DR

This paper introduces methods to measure distances between mutation trees, addresses the computational complexity of finding consensus trees, and proposes algorithms for efficient approximation and improved consensus solutions.

Contribution

It presents an efficient approach to compute distances between mutation trees, analyzes the NP-completeness of median and closest tree problems, and develops algorithms for consensus tree estimation.

Findings

Proposed a distance measure based on swap operations for trees.

Proved median and closest tree problems are NP-complete.

Developed algorithms that produce better consensus trees than input sets.

Abstract

The mutational heterogeneity of tumours can be described with a tree representing the evolutionary history of the tumour. With noisy sequencing data there may be uncertainty in the inferred tree structure, while we may also wish to study patterns in the evolution of cancers in different patients. In such situations, understanding tree similarities is a key challenge, and therefore we present an approach to determine distances between trees. Considering the bounded height of trees, we determine the distances associated with the swap operations over strings. While in general, by solving the {\sc Maximum Common Almost $v$-tree} problem between two trees, we describe an efficient approach to determine the minimum number of operations to transform one tree into another. The inherent noise in current statistical methods for constructing mutation evolution trees of cancer cells presents a significant challenge: handling such collections of trees to determine a consensus tree that accurately represents the set and evaluating the extent of their variability or dispersion. Given a set of mutation trees and the notion of distance, there are at least two natural ways to define the ``target'' tree, such as a min-sum (\emph{median tree}) or a min-max (\emph{closest tree}) of a set of trees. Thus, considering a set of trees as input and dealing with the {\sc median} and {\sc closest} problems, we prove that both problems are \NP-complete, even with only three input trees. In addition, we develop algorithms to obtain upper bounds on the median and closest solutions, which are analysed by the experiments presented on generated and on real databases. We show a fast way to find consensus trees with better results than any tree in the input set while still preserving all internal structure.