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Sapling: Inferring and Summarizing Tumor Phylogenies from Bulk Data using Backbone Trees

Qi, Y.; El-Kebir, M.

2024-04-14 cancer biology
10.1101/2024.04.10.588891 bioRxiv
Show abstract

Cancer phylogenies are key to understanding tumor evolution. There exists many important downstream analyses that takes as input a single or small number of trees. However, due to uncertainty, one typically infers many, equally-plausible phylogenies from bulk DNA sequencing data of tumors. We introduce Sapling, a heuristic method to solve the Backbone Tree Inference from Reads problem, which seeks a small set of backbone trees on a smaller subset of mutations that collectively summarize the entire solution space. Sapling also includes a greedy algorithm to solve the Backbone Tree Expansion from Reads problem, which aims to expand an inferred backbone tree into a full tree. We prove that both problems are NP-hard. On simulated and real data, we demonstrate that Sapling is capable of inferring high-quality backbone trees that adequately summarize the solution space and that can expanded into full trees.

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