Statistical Methods for ODE Models in AIDS Research

 描述(由申请人提供)：由于高通量技术的成本显著降低，在最近的艾滋病毒/艾滋病研究和其他生物医学项目中，除了收集时间进程细胞水平和纵向表型反应数据外，还经常收集频繁的时间进程全基因组基因表达数据。然而，由于缺乏重建高维动态模型的统计方法，有效地利用转录组和蛋白质组水平的高通量时间历程数据来研究动态响应和网络特征往往受到阻碍。在这个更新项目中，我们打算填补这一空白，并提出以下具体目标：1)发展更有效的高维常微分方程(ODE)模型的参数估计方法。目的1旨在发展更有效的统计方法来估计高维ODE模型参数，为在基因、蛋白质和分子水平上重建生物网络提供基础。2)发展新的高维常微分方程组变量选择的统计方法和实现步骤，以重建动态网络。我们结合了新的ODE模型统计估计方法和基于正则化的变量选择技术来识别ODE网络边缘。将为拟议的基于ODE的网络模型建立统计方法和理论依据。3)使用计算机模拟和艾滋病毒/艾滋病研究的实际数据分析，评估和验证AIMS 1-2中制定的方法。重要的是要仔细评估目标1-2中发展的高维常微分方程组变量选择和参数估计方法，并与实际使用的现有方法进行比较。特别是，有必要将拟议的方法应用于艾滋病毒/艾滋病研究的实验数据，以证明拟议的方法在解决科学问题方面的有效性。4)为提议的方法开发并向更广泛的研究界传播高效的计算算法和用户友好的软件工具。开发高效的计算算法并将计算源代码共享/分发给一般研究社区是非常重要的。

 DESCRIPTION (provided by applicant): Owing to the significant cost reduction of high-throughput technologies, frequent time course genome-wide gene expression data, in addition to time course cellular level and longitudinal phenotype response data, are often collected in recent HIV/AIDS studies and other biomedical projects. However, the effective use of the high-throughput time course data at transcriptomic and proteomics levels to study dynamic responses and network features is often hindered by lacking of statistical methods to reconstruct high-dimensional dynamic models. In this renewal project, we intend to fill this gap and propose the following specific aims: 1) Develop more efficient parameter estimation methods for high-dimensional ordinary differential equation (ODE) models. Aim 1 intends to develop more efficient statistical methods to estimate high-dimensional ODE model parameters to provide a foundation for reconstructing biological networks at gene, protein and molecular levels. 2) Develop novel statistical methods and implementation procedures for high-dimensional ODE variable selection to reconstruct the dynamic networks. We combine new statistical estimation methods for ODE models and regularization-based variable selection techniques to identify ODE network edges. Statistical methodologies and theoretical justifications will be established for the proposed ODE-based network models. 3) Evaluate and validate the methodologies developed in Aims 1-2 using computer simulations and real data analysis from HIV/AIDS studies. It is important to carefully evaluate the high-dimensional ODE variable selection and parameter estimation methods developed in Aims 1-2, and perform comparisons with existing methods for practical use. In particular, it is necessary to apply the proposed methods to experimental data from HIV/AIDS studies in order to demonstrate the usefulness of the proposed methodologies to address scientific questions. 4) Develop and disseminate efficient computational algorithms and user-friendly software tools for the proposed methods to the broader research community. It is very important to develop efficient computing algorithms and share/disseminate the computational source codes to the general research community.