Estimation of Spontaneous Mutation Rates
University of California at San DiegoSpontaneous or randomly occurring mutations play a key role in cancer
progression. Estimation of the mutation rate of cancer cells can provide
useful information about the disease.
In this investigation, we develop a discrete time stochastic model
for a mutational birth process. We assume that mutations occur concurrently
with mitosis so that when a non-mutant parent cell splits into two progeny,
one of these daughter cells could carry a mutation. We propose an estimator
for the mutation rate and investigate its statistical properties (bias and
mean-squared error) via theory and simulations. Sensitivity of the proposed
estimator to deviations from modeling assumptions are also explored.
The methods developed herein are applied to a human colorectal cancer
cell line and compared to existing continuous time models.