itNETZ: Integrative and Translational Network-based Cellular Signature Analyzer

描述(由申请人提供)：迫切需要开发系统平台，以应对综合网络蜂窝签名库(LINCS)计划快速进展带来的挑战和机遇。LINCS计划执行交叉的高通量分析，并开发针对各种干扰剂和候选药物产生的信息性分子活性和细胞特征特征的综合计算分析。拟议研究的主要目标是开发一个面向签名的软件平台--基于综合和翻译网络的蜂窝签名分析器(ItNETZ)，以满足这一需求。该系统的工作流程是：1)识别疾病和药物特定的分子和细胞特征，2)揭示这些特征的组件之间的机制关联并将它们描绘为信号和调节网络，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特征，5)发现跨细胞系和疾病的共同特征和网络，6)建立和维护治疗反应的公共资源，以及7)促进研究界查询兴趣特征，探索特征之间的相关性，以及产生假设。该系统将实现以下功能：第一，用于处理细胞图像、Luminex基因组数据、转录组测序数据以及磷蛋白信号通路建模的基本分析和发现工具包；第二，数据整合和挖掘工具包，用于将基因组和蛋白质组学映射到细胞表型，用于识别不同抑制剂处理的细胞系的核心通路标志和药物诱导的通路标志变化，以及用于构建药物动态组景观。ItNETZ系统包括加载输入、分析图像、处理基因组和蛋白质组数据、将输出导出到关系数据库、集成和挖掘数据以及生成感兴趣的基于网络的细胞签名的管道。基于XML的协议将用于数据交换。

DESCRIPTION (provided by applicant): There is an urgent need to develop systematic platforms to address the challenges and opportunities brought forth by the fast progresses of the 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 of the 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 of the 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 of interest. XML-based protocols will be used for data exchanging.