Document Type

Article

Publication Date

1-1-2017

Publication Title

PLoS One

Keywords

Bayes Theorem; Carcinogenesis; Colorectal Neoplasms; Computer Simulation; DNA Copy Number Variations; DNA Methylation; Genetic Heterogeneity; Humans; Microsatellite Repeats; Mutation; Neoplastic Stem Cells

Abstract

Tumor growth is an evolutionary process involving accumulation of mutations, copy number alterations, and cancer stem cell (CSC) division and differentiation. As direct observation of this process is impossible, inference regarding when mutations occur and how stem cells divide is difficult. However, this ancestral information is encoded within the tumor itself, in the form of intratumoral heterogeneity of the tumor cell genomes. Here we present a framework that allows simulation of these processes and estimation of mutation rates at the various stages of tumor development and CSC division patterns for single-gland sequencing data from colorectal tumors. We parameterize the mutation rate and the CSC division pattern, and successfully retrieve their posterior distributions based on DNA sequence level data. Our approach exploits Approximate Bayesian Computation (ABC), a method that is becoming widely-used for problems of ancestral inference.

Clinical Institute

Cancer

Department

Oncology

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