Statistical inference of the rates of cell proliferation and phenotypic switching in cancer

DOI10.1016/J.JTBI.2023.111497MaRDI QIDQ6174231zbMATH OpenFDO

Authors Einar Bjarki Gunnarsson, Jasmine Foo, Kevin Leder

Publication date 14 July 2023

Published in Journal of Theoretical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/2306.08096

zbMATH Keywords

maximum likelihood estimationmathematical modelingphenotypic switchingparameter identifiabilityepigeneticscancer evolution

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Developmental biology, pattern formation (92C15) Pathology, pathophysiology (92C32)

Abstract: Recent evidence suggests that nongenetic (epigenetic) mechanisms play an important role at all stages of cancer evolution. In many cancers, these mechanisms have been observed to induce dynamic switching between two or more cell states, which commonly show differential responses to drug treatments. To understand how these cancers evolve over time, and how they respond to treatment, we need to understand the state-dependent rates of cell proliferation and phenotypic switching. In this work, we propose a rigorous statistical framework for estimating these parameters, using data from commonly performed cell line experiments, where phenotypes are sorted and expanded in culture. The framework explicitly models the stochastic dynamics of cell division, cell death and phenotypic switching, and it provides likelihood-based confidence intervals for the model parameters. The input data can be either the fraction of cells or the number of cells in each state at one or more time points. Through a combination of theoretical analysis and numerical simulations, we show that when cell fraction data is used, the rates of switching may be the only parameters that can be estimated accurately. On the other hand, using cell number data enables accurate estimation of the net division rate for each phenotype, and it can even enable estimation of the state-dependent rates of cell division and cell death. We conclude by applying our framework to a publicly available dataset.

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Cites work

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Cited in

(4)

• Parameter estimation from single patient, single time-point sequencing data of recurrent tumors
• A Bayesian statistical analysis of stochastic phenotypic plasticity model of cancer cells
• Inferring density-dependent population dynamics mechanisms through rate disambiguation for logistic birth-death processes
• Mathematical modeling and dynamic analysis for cancer resistance incorporating persister cells

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