Markov models for accumulating mutations

DOI10.1093/BIOMET/ASP023MaRDI QIDQ3399077zbMATHOpenAlexFDO

Authors Niko Beerenwinkel, Seth Sullivant

Publication date 29 September 2009

Published in Biometrika (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/0709.2646

zbMATH Keywords

cancerBayesian networkHIVpartially ordered setposetgenetic progression

Mathematics Subject Classification ID

Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Medical applications (general) (92C50) Genetics and epigenetics (92D10) Diffusion processes (60J60)

Abstract: We introduce and analyze a waiting time model for the accumulation of genetic changes. The continuous time conjunctive Bayesian network is defined by a partially ordered set of mutations and by the rate of fixation of each mutation. The partial order encodes constraints on the order in which mutations can fixate in the population, shedding light on the mutational pathways underlying the evolutionary process. We study a censored version of the model and derive equations for an EM algorithm to perform maximum likelihood estimation of the model parameters. We also show how to select the maximum likelihood poset. The model is applied to genetic data from different cancers and from drug resistant HIV samples, indicating implications for diagnosis and treatment.

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Cited in

(13)

• Maximum likelihood estimation of oncogenetic tree models
• Cumulative disease progression models for cross-sectional data: a review and comparison
• Pseudo-Marginal Inference for CTMCs on Infinite Spaces via Monotonic Likelihood Approximations
• Low-rank tensor methods for Markov chains with applications to tumor progression models
• A basic model of mutations
• Waiting time models of cancer progression
• Waiting times to appearance and dominance of advantageous mutants: Estimation based on the likelihood
• Discrete max-linear Bayesian networks
• Model Selection for Mixtures of Mutagenetic Trees
• Conjunctive Bayesian networks
• Detection of significant genomic alterations via simultaneous minimal sojourns at a state by independent continuous-time Markov chains
• Learning monotonic genotype-phenotype maps
• Microsatellite evolution: Markov transition functions for a suite of models

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