PCI Math Comp Biol

112

Title *

Cancer phylogenetic tree inference at scale from 1000s of single cell genomesuse asterix (*) to get italics

Authors *

Sohrab Salehi, Fatemeh Dorri, Kevin Chern, Farhia Kabeer, Nicole Rusk, Tyler Funnell, Marc J Williams, Daniel Lai, Mirela Andronescu, Kieran R. Campbell, Andrew McPherson, Samuel Aparicio, Andrew Roth, Sohrab Shah, and Alexandre Bouchard-CôtéPlease use the format "First name initials family name" as in "Marie S. Curie, Niels H. D. Bohr, Albert Einstein, John R. R. Tolkien, Donna T. Strickland"

Year *

2023

Picture *

Abstract *

A new generation of scalable single cell whole genome sequencing (scWGS) methods allows unprecedented high resolution measurement of the evolutionary dynamics of cancer cell populations. Phylogenetic reconstruction is central to identifying sub-populations and distinguishing the mutational processes that gave rise to them. Existing phylogenetic tree building models do not scale to the tens of thousands of high resolution genomes achievable with current scWGS methods. We constructed a phylogenetic model and associated Bayesian inference procedure, Sitka, specifically for scWGS data. The method is based on a novel phylogenetic encoding of copy number (CN) data, the Sitka transformation, that simplifies the site dependencies induced by rearrangements while still forming a sound foundation to phylogenetic inference. The Sitka transformation allows us to design novel scalable Markov chain Monte Carlo (MCMC) algorithms. Moreover, we introduce a novel point mutation calling method that incorporates the CN data and the underlying phylogenetic tree to overcome the low per-cell coverage of scWGS. We demonstrate our method on three single cell datasets, including a novel PDX series, and analyse the topological properties of the inferred trees. Sitka is freely available at \href{https://github.com/UBC-Stat-ML/sitkatree.git}{https://github.com/UBC-Stat-ML/sitkatree.git}.

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Keywords (optional)

Phylogenetics, Evolutionary dynamics, Single cell genomics, Cancer evolution, scalable Bayesian inference

Methods that require specific expertise (optional)

NonePlease indicate the methods that may require specialised expertise during the peer review process (use a comma to separate various required expertises).

Thematic fields *

Evolutionary Biology, Genetics and population Genetics, Genomics and Transcriptomics, Machine learning, Probability and statistics

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Submission date

2021-12-10 17:08:04

Recommender

Amaury Lambert

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