title: Early mutation bursts in colorectal tumors.
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.
authors.affiliation: Department of Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Junsong
authors.identifier: http://orcid.org/0000-0001-5167-1363
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, United States of America.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Salomon
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Darryl
authors.initials: D
authors.lastname: Shibata
authors.affiliation: Department of Medicine (Oncology) and Genetics, School of Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Curtis
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Siegmund
authors.affiliation: Department of Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America.|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Marjoram
mesh_terms: D001499:Bayes Theorem; D063646:Carcinogenesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003198:Computer Simulation; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D018740:Genetic Heterogeneity; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000473:pathology