itNETZ: Integrative and Translational Network-based Cellular Signature Analyzer

itNETZ：基于集成和翻译网络的细胞特征分析仪

• 批准号: 8336886
• 负责人: Xiaobo Zhou
• 金额: $ 17.07万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-24 至 2013-04-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8336886
• 关键词: Address; Cell Line; Cell physiology; Cells; Classification; Clinical; Collaborations; Communities; Computer Analysis; Computer software; Data; Data Analyses; Diffusion; Disease; Drug Delivery Systems; Education; Ensure; Extensible Markup Language; Future; Gene Expression Profile; Gene Mutation; Generations; Genes; Genomics; Goals; Graph; Hybrids; Imagery; Instruction; Internet; Knowledge; Libraries; Life; Ligands; Maps; Mass Spectrum Analysis; Metric; Modeling; Molecular; Mutation; Nature; Network-based; Output; Pathway interactions; Pharmaceutical Preparations; Phase; Phenotype; Phosphoproteins; Physicians; Process; Proteomics; Protocols documentation; Public Health; Research; Resources; Screening procedure; Signal Pathway; Signal Transduction; Source; System; Therapeutic; Training Programs; Training Support; Tumor Biology; Work; base; cell behavior; cell type; cellular imaging; computerized data processing; data exchange; data format; data integration; data mining; data modeling; design; drug candidate; drug mechanism; high throughput screening; image processing; in vivo; inhibitor/antagonist; insight; interest; mathematical model; medical specialties; novel; novel strategies; programs; receptor; relational database; response; tool; vector

There is an urgent need to develop systematic platforms to address the challenges and opportunities brought forth by the fast progresses ofthe Library of Integrated Network-Based Cellular Signatures (LINCS) program. The LINCS program performs cross-cutting high-throughput assays and develops integrative computational analysis of informative molecular activity and cellular feature signatures generated in response to a variety of perturbing agents and drug candidates. The primary goal of the proposed study is to address the needs by developing a signature-oriented software platform, the Integrative and Translational Network-based Cellular Signature Analyzer (itNETZ). The working flow ofthe system is: 1) to identify disease- and drug-specific molecular and cellular features, 2) to reveal the mechanismistic associations between components of such features and delineate them as signaling and regulating networks, 3) to present the dynamics of such networks by mathematical models, 4) to construct network-based molecular and cellular signatures, 5) to discover common signatures and networks across cell lines and diseases, 6) to establish and maintain a public resource ofthe increasing resultant knowledge of therapeutic responses, and 7) to facilitate the research community on querying signatures of interests, exploring correlations among signatures, and generating hypotheses. This system will enable the following functions: first, the basic analysis and discovery toolkits for processing cellular images, Luminex genomics data, transcriptome sequencing data, and for modeling phosphoproteins signaling pathway; and second, data integration and mining toolkits for mapping genomics and proteomics to cellular phenotypes, for core pathway signature identification on cell lines treated by different inhibitors and drug-induced pathway signature alterations, and for constructing drug kinome landscapes. The itNETZ system comprises pipelines that load input, analyze images, process genomics and proteomics data, export outputs into a relational database, integrate and mine the data, and generate network-based cellular signatures ofinterest. XML-based protocols will be used for data exchanging.

迫切需要建立系统平台，以应对挑战和机遇 基于网络的综合细胞签名库（LINCS）的快速发展所带来的 程序. LINCS项目进行交叉高通量检测，并开发集成的 信息分子活性和细胞特征签名的计算分析， 对各种干扰剂和候选药物的反应。 拟议研究的主要目标是通过制定一个以签名为导向的 软件平台，集成和翻译基于网络的蜂窝签名分析仪（itNETZ）。 该系统的工作流程是：1）识别疾病和药物特异性的分子和细胞特征，2） 揭示这些特征的组成部分之间的机制联系，并将它们描述为 信令和调节网络，3）通过数学模型呈现这种网络的动态，4） 构建基于网络的分子和细胞签名，5）发现共同签名， 跨细胞系和疾病的网络，6）建立和维护不断增加的公共资源 由此产生的治疗反应的知识，和7），以促进研究界查询 感兴趣的签名，探索签名之间的相关性，并生成假设。 该系统将实现以下功能：首先， 处理细胞图像、Luminex基因组数据、转录组测序数据并进行建模 磷蛋白信号通路;第二，用于绘制基因组学的数据集成和挖掘工具包 和蛋白质组学应用于细胞表型，用于对经以下处理的细胞系进行核心途径签名鉴定： 不同的抑制剂和药物诱导的途径签名改变，并用于构建药物激酶组 的风景. itNETZ系统包括加载输入、分析图像、处理基因组学和 蛋白质组学数据，将输出导出到关系数据库，整合和挖掘数据，并生成 基于网络的蜂窝签名。基于XML的协议将用于数据交换。