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A systematic approach to determining the identifiability of multistage carcinogenesis models

机译:确定多阶段致癌模型可识别性的系统方法

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摘要

Multistage clonal expansion (MSCE) models of carcinogenesis are continuous-time Markov process models often used to relate cancer incidence to biological mechanism. Identifiability analysis determines what model parameter combinations can, theoretically, be estimated from given data. We use a systematic approach, based on differential algebra methods traditionally used for deterministic ODE models, to determine identifiable combinations for a generalized subclass of MSCE models with any number of pre-initation stages and one clonal expansion. Additionally, we determine the identifiable combinations of the generalized MSCE model with up to four clonal expansion stages, and conjecture the results for any number of clonal expansion stages. The results improve upon previous work in a number of ways and provide a framework to find the identifiable combinations for further variations on the MSCE models. Finally, our approach, which takes advantage of the Kolmogorov backward equations for the probability generating functions of the Markov process, demonstrates that identifiability methods used in engineering and mathematics for systems of ODES can be applied to continuous-time Markov processes.
机译:致癌作用的多阶段克隆扩展(MSCE)模型是连续时间马尔可夫过程模型,通常用于将癌症发病率与生物学机制联系起来。可识别性分析确定了理论上可以从给定数据中估算出哪些模型参数组合。我们使用一种系统化的方法,基于传统上用于确定性ODE模型的微分代数方法,来确定具有多个预激发阶段和一个克隆扩展的MSCE模型的广义子类的可识别组合。此外,我们确定了具有多达四个克隆扩展阶段的广义MSCE模型的可识别组合,并推测了任意数量的克隆扩展阶段的结果。结果以多种方式改进了先前的工作,并提供了一个框架,以找到可识别的组合,以进一步对MSCE模型进行更改。最后,我们的方法利用了Kolmogorov向后方程的马尔可夫过程的概率生成函数,证明了在ODES系统的工程和数学中使用的可识别性方法可以应用于连续时间的马尔可夫过程。

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