基于分支理论的组合摄动分析及其应用

发布时间：2018-04-23 02:36

本文选题：分支理论 + 组合摄动　；参考：《上海大学》2016年博士论文

【摘要】：针对生物分子网络、生物功能、疾病的发展及治疗领域中涉及的组合调控和组合药物问题,提出一种基于分支理论的组合摄动研究方法,用于分析组合调控对系统动力学的影响。与已有的用于评价组合摄动效率的方法相比较,该方法由于不涉及系统对刺激响应的暂态动力学,所以大幅减少了计算量,简化了分析的过程,并且在生物功能调控,细胞命运决策和组合药物治疗方面有着重要的应用价值。我们运用基于分支理论的组合摄动方法调查了HBV/HDV感染在组合药物PEG-IFNα和nucleos/tide analogues治疗下的动力学演变,由此分析这两种药物在治疗中的协同调控作用,并结合实际的临床试验报道,来分析该组合药物在治疗HBV/HDV感染中所表现出来的个体差异性。本论文的主要研究内容为第3和第4部分,详情如下：1)针对生物分子网络和组合药物治疗中的组合调控问题,分析提出基于分支理论的组合摄动研究方法的实际意义及合理性,并借助于一个多稳决策模型给出基于动力学分支的组合摄动方法的理论推导和定义。同时通过分析目标函数与组合摄动之间的关系,我们也研究了组合摄动的最优组合策略。为了验证该方法的有效性和计算的简便性,我们运用此方法研究一个生物上现实的CREB模型,并与已有的组合摄动方法的结论进行比较。2)结合免疫响应机制发展了一种HBV/HDV感染模型,利用稳定性理论和分支理论分别研究了该模型平衡点的局部稳定性和模型动力学在单药物或组合药物治疗下的演变过程。运用我们所提出来的基于分支的组合摄动理论研究组合药物PEG-IFN a与nucleos/tide analogues在治疗]HBV/HDV感染中所表现出来的协同调控性,并结合免疫响应机制分析治疗中所出现的疗效个体差异。
[Abstract]:Aiming at the problems of combinatorial regulation and combinatorial drugs involved in the field of biomolecules network, biological function, disease development and treatment, a method of combinatorial perturbation research based on branch theory is proposed. It is used to analyze the effect of combinatorial regulation on system dynamics. Compared with the existing methods for evaluating the combined perturbation efficiency, the proposed method greatly reduces the computational complexity, simplifies the analysis process and regulates the biological function because it does not involve the transient dynamics of the system's response to the stimuli. Cell fate decision and combination drug therapy have important application value. We investigated the dynamic evolution of HBV/HDV infection under the treatment of PEG-IFN 伪 and nucleos/tide analogues by using the combined perturbation method based on branch theory, and analyzed the synergistic effect of these two drugs in the treatment, and combined with the actual clinical trial report. To analyze the individual differences of the combination in the treatment of HBV/HDV infection. The main contents of this thesis are the third and fourth parts. The details are as follows: (1) aiming at the problem of combinatorial regulation in biomolecules network and combinatorial drug therapy, the practical significance and rationality of the combined perturbation research method based on branch theory are analyzed. The theoretical derivation and definition of the combined perturbation method based on dynamic bifurcation are given by means of a multistable decision model. At the same time, by analyzing the relationship between the objective function and the combined perturbation, we also study the optimal combination strategy of the combined perturbation. In order to verify the validity and simplicity of the method, we use this method to study a biologically realistic CREB model. A HBV/HDV infection model was developed in combination with immune response mechanism. The stability theory and branch theory are used to study the local stability of the equilibrium point and the evolution of the model dynamics under the treatment of single drug or combination drug, respectively. Using the branch-based combination perturbation theory proposed by us, we studied the synergistic regulation of PEG-IFN a and nucleos/tide analogues in the treatment of HBV/HDV infection, and analyzed the individual differences of therapeutic efficacy in combination with the immune response mechanism.
【学位授予单位】：上海大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R91

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