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Integrating Top-Down and Bottom-Up Models in Systems Biology with Application to

在系统生物学中整合自上而下和自下而上的模型并应用于

基本信息

批准号：
8257897
负责人：
T M Murali
金额：
$ 37.55万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8257897
关键词：
Algorithms Apoptosis Attention Automobile Driving Bacteriophages Beds Binding Biological Biological Process Cell Cycle Cell Cycle Regulation Cell division Cell model Cell physiology Cells Chemotaxis Communicable Diseases Complex Computers Data Data Set Databases Development Environment Escherichia coli Experimental Designs Feedback Gene Expression Gene Expression Profile Gene Proteins Generations Genes Genetic Genome Genotype Graph Hand Life Link Literature Macromolecular Complexes Malignant Neoplasms Maps Messenger RNA Metabolic Methodology Methods Modeling Molecular Movement Pattern Phenotype Physiological Processes Property Proteome Regulation Saccharomycetales Signal Transduction Simulate System Systems Biology Testing Validation Yeast Model System Yeasts cell growth data mining design flexibility interest mutant novel predictive modeling protein metabolite public health relevance repository response success tool

项目摘要

DESCRIPTION (provided by applicant): Project Summary Two distinct approaches are being used to study complex cellular systems. The first approach automatically searches large datasets for correlations between genes and proteins and represents these as a graph with nodes and edges. The second approach painstakingly crafts detailed models that can be simulated by computer. These approaches have largely been developed separately until now. This project will meld these two approaches into a single framework, thereby allowing fast database searches to augment models that can be simulated. Specifically, the project will 1. Develop fast algorithms to search databases of molecular data to suggest extensions to models of cellular control systems 2. Develop new principles to test how well these extended models match experimental data and 3. Design experimental tests that can validate the predictions made by the first two steps. The project will validate this system by studying the mechanism of cell division, a system involved in the development of cancer. In the long term, the methods developed by this project can be used to study any complex cellular system, e.g., those implicated in infectious diseases. PUBLIC HEALTH RELEVANCE: Project Narrative This project will meld two distinct approaches for studying complex cellular systems, one top-down and the other bottom-up, into a single framework. The project will combine the power of fast database searches with hand-crafted models. The project will validate this system by studying the mechanism of cell division, a system involved in the development of cancer.

描述（由申请人提供）：两种不同的方法被用于研究复杂的细胞系统。第一种方法自动搜索基因和蛋白质之间相关性的大型数据集，并将其表示为具有节点和边的图。第二种方法是精心制作可以用计算机模拟的详细模型。到目前为止，这些方法在很大程度上是单独开发的。该项目将把这两种方法融合到一个框架中，从而允许快速的数据库搜索来增强可以模拟的模型。具体而言，该项目将1。开发快速算法来搜索分子数据的数据库，以建议细胞控制系统模型的扩展2。开发新的原则来测试这些扩展模型与实验数据的匹配程度，3.设计实验测试，以验证前两步所做的预测。该项目将通过研究细胞分裂的机制来验证这一系统，细胞分裂是一个参与癌症发展的系统。从长远来看，该项目开发的方法可用于研究任何复杂的细胞系统，例如，那些与传染病有关的人公共卫生相关性：该项目将把两种不同的研究复杂蜂窝系统的方法，一种是自上而下，另一种是自下而上，融合到一个框架中。该项目将结合联合收割机的快速数据库搜索与手工制作的模型的力量。该项目将通过研究细胞分裂的机制来验证这一系统，细胞分裂是一个参与癌症发展的系统。