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反应网络中的疾病演变:对诊断问题的启示。

Disease evolution in reaction networks: Implications for a diagnostic problem.

机构信息

Medical Systems Biophysics and Bioengineering, Leiden Academic Centre for Drug Research, Faculty of Science, Leiden University, Leiden, The Netherlands.

Physics Department, College of Sciences, Shiraz University, Shiraz, Iran.

出版信息

PLoS Comput Biol. 2020 Jun 4;16(6):e1007889. doi: 10.1371/journal.pcbi.1007889. eCollection 2020 Jun.

Abstract

We study the time evolution of symptoms (signs) with some defects in the dynamics of a reaction network as a (microscopic) model for the progress of disease phenotypes. To this end, we take a large population of reaction networks and follow the stochastic dynamics of the system to see how the development of defects affects the macroscopic states of the signs probability distribution. We start from some plausible definitions for the healthy and disease states along with a dynamical model for the emergence of diseases by a reverse simulated annealing algorithm. The healthy state is defined as a state of maximum objective function, which here is the sum of mutual information between a subset of signal variables and the subset of assigned response variables. A disease phenotype is defined with two parameters controlling the rate of mutations in reactions and the rate of accepting mutations that reduce the objective function. The model can provide the time dependence of the sign probabilities given a disease phenotype. This allows us to obtain the accuracy of diagnosis as a function of time by using a probabilistic model of signs and diseases. The trade-off between the diagnosis accuracy (increasing in time) and the objective function (decreasing in time) can be used to suggest an optimal time for medical intervention. Our model would be useful in particular for a dynamical (history-based) diagnostic problem, to estimate the likelihood of a disease hypothesis given the temporal evolution of the signs.

摘要

我们研究了反应网络动力学中的一些缺陷对症状(体征)时间演化的影响,将其作为疾病表型进展的(微观)模型。为此,我们采用大量反应网络,跟踪系统的随机动力学,观察缺陷的发展如何影响体征概率分布的宏观状态。我们从健康和疾病状态的一些合理定义以及通过反向模拟退火算法出现疾病的动力学模型开始。健康状态定义为目标函数最大的状态,这里的目标函数是信号变量子集和分配的响应变量子集之间互信息的总和。疾病表型由两个参数控制,即反应突变率和接受降低目标函数的突变率。该模型可以为给定疾病表型的体征概率提供时间依赖性。这允许我们通过使用体征和疾病的概率模型来获得随时间变化的诊断准确性。诊断准确性(随时间增加)和目标函数(随时间减少)之间的权衡可以用于建议进行医学干预的最佳时间。我们的模型对于动态(基于历史的)诊断问题特别有用,可用于根据体征的时间演化来估计疾病假设的可能性。

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