Core F & G: Systems/Modeling & Computation

核心F

基本信息

批准号：
8126760
负责人：
Srinivas Ravi V Iyengar
金额：
$ 31.14万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8126760
关键词：
Accounting Address Adopted Adverse effects Adverse event Animal Model Behavior Biological Biological Models Biological Process Cell Lineage Clinical Communities Complement Computer Simulation Confidentiality of Patient Information Data Data Analyses Data Set Databases Development Disease Dose Drug Formulations Drug Kinetics Drug effect disorder Education Eicosanoids Elements Event Experimental Designs Experimental Models Funding Genetic Genomics Homologous Gene Human Human Biology Imagery Individual Intuition Language Link Lipids Machine Learning Maps Methods Modeling Molecular Mus Network-based Non-Steroidal Anti-Inflammatory Agents Organ Organism Outcome Output Pathway interactions Patients Pharmaceutical Preparations Pharmacology Phenotype Physiological Population Process Proteins Quality Control RNA Splicing Regimen Risk Scientist Signal Transduction Specific qualifier value Specificity Sum System Systems Biology Testing Therapeutic Effect Tissues Translating Treatment Efficacy Update Variant base computerized data processing dosage flexibility insight microbiome network models pharmacokinetic model research study response simulation small molecule

项目摘要

A central challenge for PENTACON in identifying molecular-level causes of NSAID-specificity with respect to efficacy vs. adverse effects is the integrative computational modeling of the activity of the diverse cellular components that are perturbed upon NSAID administration. It is in these two cores that integrate our approaches to systems biology and modeling. In the Systems, Modeling and Computation Cores we describe how PENTACON will produce an outcome that is greater than the sum its component parts. We will use network-based discrete and dynamic computational models to integratively model behavior and functional conservation of diverse biomolecules, accounting for cell-lineage and environmental effects in the context of genomic and environmental variation. We are aware of the levels of complexity in this system that we may not be directly modeling. Indeed, some elements may even violate our assumptions, for example splice variants and discrete impacts of the epigenome. We address these challenges through (1) a combination of diverse approaches, including exploratory studies (such as for microbiome data) and (2) directed modeling efforts and close iteration of modeling and experimental verification with quantitative functional outputs that translate directly to humans. We will also adopt a flexible approach, updating the modeling approaches to information that emerges from our analyses.

Pentacon在识别NSAID特异性的分子级原因方面的核心挑战功效与不良反应是多种细胞活性的整合计算建模对NSAID管理的组件。正是在这两个核心中系统生物学和建模的方法。在系统，建模和计算核心中描述Pentacon将如何产生大于其组成部分总和的结果。我们将使用基于网络的离散和动态计算模型来整合模型行为和功能在各种生物分子的保护下，占细胞限制和环境影响的背景下基因组和环境变化。我们知道该系统中的复杂程度，我们可能不会直接建模。确实，某些要素甚至可能违反我们的假设，例如剪接变体和表观基因组的离散影响。我们通过（1）多样化解决这些挑战方法，包括探索性研究（例如微生物组数据）和（2）指示建模工作和与定量功能输出的建模和实验验证的关闭迭代直接对人类。我们还将采用灵活的方法，将建模方法更新到信息这是从我们的分析中得出的。