Statistical Methods for ODE Models in AIDS Research

艾滋病研究中 ODE 模型的统计方法

• 批准号: 9268717
• 负责人: Hulin Wu
• 金额: $ 34.65万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9268717
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Algorithms; Area; Basic Science; Biological; Biomedical Research; Biomedical Technology; Blood; CD8-Positive T-Lymphocytes; Cell Line; Communities; Complex; Computational algorithm; Computer Simulation; Data; Data Analyses; Differential Equation; Disease Progression; Epidemic; Foundations; Funding Agency; Gene Expression; Gene Proteins; Genetic; Genetic Transcription; Genomics; HIV; HIV Infections; HIV vaccine; HIV-1; Highly Active Antiretroviral Therapy; Immune system; Immunologics; Infection; Investments; Life; Macaca; Macaca mulatta; Messenger RNA; Metabolic Pathway; Methodology; Methods; MicroRNAs; Modeling; Molecular; Network-based; Pathogenesis; Phenotype; Procedures; Proteins; Proteomics; Regulator Genes; Research; Research Personnel; SIV; Signal Transduction; Software Framework; Software Tools; Source Code; Statistical Methods; Systems Biology; T-Lymphocyte; Techniques; Therapeutic; Time; United States National Institutes of Health; Vaccination; Vaccines; Viral Load result; Virus; base; biological systems; cost; deep sequencing; design; experimental study; genome-wide; high dimensionality; high throughput screening; high throughput technology; immunogenicity; mathematical model; metabolomics; network models; new technology; nonhuman primate; novel; pathogen; public health relevance; response; temporal measurement; time use; transcriptome sequencing; transcriptomics; user friendly software; vaccine development; vector vaccine

 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.

 描述（由申请人提供）：由于高通量技术的成本显着降低，在最近的艾滋病毒/艾滋病研究和其他生物医学项目中，除了时程细胞水平和纵向表型反应数据之外，还经常收集时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，有效利用转录组和蛋白质组水平的高通量时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）为高维常微分方程（ODE）模型开发更有效的参数估计方法。目标1旨在开发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）开发新的统计方法和执行程序，用于高维ODE变量选择以重建动态网络。我们结合 ODE 模型的新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。将为所提出的基于 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/艾滋病研究的真实数据分析来评估和验证目标 1-2 中开发的方法。仔细评估目标 1-2 中开发的高维 ODE 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非常重要。特别是，有必要将所提出的方法应用于艾滋病毒/艾滋病研究的实验数据，以证明所提出的方法在解决科学问题方面的有用性。 4) 为所提出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向一般研究社区共享/传播计算源代码非常重要。