Markov models for accumulating mutations

DOI10.1093/BIOMET/ASP023zbMATH Open1170.62076arXiv0709.2646OpenAlexW2059684559MaRDI QIDQ3399077FDOQ3399077

Authors: Niko Beerenwinkel, Seth Sullivant 

Publication date: 29 September 2009

Published in: Biometrika (Search for Journal in Brave)

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.

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

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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)

Cited In (13)

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

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