Elucidation of Functional Networks from Toxicogenomics Gene Expression Data

从毒理基因组学基因表达数据阐明功能网络

基本信息

批准号：
7270351
负责人：
TATIANA A NIKOLSKAYA
金额：
$ 40.52万
依托单位：
GENEGO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-10 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7270351
关键词：
Academia Academy Accounting Algorithms Animal Model Area Award Biological Biological Markers Capital Categories Cell physiology Class Clinic Clinical Research Computer software Condition Data Data Analyses Data Reporting Data Set Databases Descriptor Development Disease Drug Industry Drug effect disorder Environmental Health Evaluation Funding Gene Expression Generations Genes Genomics Grant Human Biology Industry Institutes Intramural Research Investments Laboratories Libraries Licensing Methods Molecular Profiling Pathway interactions Pattern Pharmaceutical Preparations Pharmacologic Substance Phase Process Proteomics Protocols documentation Public Domains Publications Publishing Reporting Research Small Business Funding Mechanisms Small Business Innovation Research Grant Small Interfering RNA System Technology Today Toxic effect Toxicogenomics United States Food and Drug Administration United States National Institutes of Health Universities Yeasts base data mining design drug development high throughput analysis human disease interest metabolomics novel novel strategies pre-clinical research response tool

项目摘要

DESCRIPTION (provided by applicant): In Phase I, we have developed a novel approach to the analysis of toxicogenomics data based on functional categorization and signature networks. The method enables identification of pathways and biological networks most different between gene expression response to drug action, and it can be applied for categorization of molecular profiles by toxicity categories. We have also functional profiling on a large dataset of hepatotoxic compounds from CEBS database. In Phase II, we propose to formalize the new approach in algorithms and build a semi-automated module for generation of signature networks specific for a toxicity type. We will also build a reference database of quantitative functional descriptors for toxic categories which can be used for categorizing of molecular profiles for novel compounds. We will develop a workflow for functional analysis of toxicogenomics datasets and a reporting protocol which sponsor companies can use for voluntary submission of toxicogenomics data to FDA and the reviewers for evaluation of the submitted data. Finally, we propose to build a novel integrated platform for functional data mining of toxicogenomics data and reporting, MetaTox. MetaTox will include the manually curated database of human biology created at GeneGo, a general datamining toolkit (networks, pathways, cellular processes, disease and toxicity categories), pre-processed toxicogenomics data from public domain, and the tools created in the scope of this project (signature networks module and the database of functional descriptors for toxicity categories). In Phase II, we propose to complete the set of tools and workflows for functional analysis of toxicogenomics data. This will include a novel module for generation and comparison of signature networks for different toxic categories, matrix of quantitative functional categories and a new toxicogenomics platform MetaTox

描述（由申请人提供）：在第一阶段，我们开发了一种基于功能分类和签名网络的毒物基因组学数据分析的新方法。该方法可以识别基因表达对药物作用的反应之间最不同的途径和生物网络，并且可以将其用于分类分子谱分类。我们还在CEBS数据库的大型肝毒性化合物数据集上进行了功能分析。在第二阶段，我们建议在算法中形式化新方法，并构建一个半自动化模块，以生成针对毒性类型的特定的签名网络。我们还将为有毒类别构建定量功能描述符的参考数据库，该数据库可用于对新化合物的分子曲线进行分类。我们将开发一个工作流程，用于对毒理学数据集的功能分析和一个报告协议，并提议公司可以将其用于自愿提交给FDA的毒理学数据和审查者评估提交数据。最后，我们建议建立一个新颖的集成平台，用于毒理基因组学数据和报告，metatox的功能数据挖掘。 Metatox将包括在Genego创建的人类生物学数据库，Genego是一个通用的数据安装工具包（网络，路径，细胞过程，疾病和毒性类别），来自公共领域的预处理毒性组学数据，以及该项目范围中创建的工具（Signature Networks模块和功能性的数据库质量毒性毒性）。在第二阶段，我们建议完成一组工具和工作流程，以进行毒理基因组学数据的功能分析。这将包括一个新的模块，用于生成和比较不同有毒类别的签名网络，定量功能类别的矩阵和一个新的毒物基因组学平台metatox