Development and Support of the Pathway Tools Software [SRI Proposal ECU 11-614]

描述（由申请人提供）：生物体（如致病细菌）基因组序列的完成标志着加速研究阶段的开始，该阶段现在可以导致生物体定量代谢通量模型的产生。这样的代谢通量模型具有不同的应用。它们使生物化学途径的基本科学理解成为可能。它们允许计算预测代谢网络中哪些基因和反应是必不可少的，从而促进针对致病细菌的药物设计。它们支持新代谢途径的工程设计，例如生物能源研究。 由基因组序列以及生物体过去和未来的大量实验发现定义的大量数据和知识需要使用数据库作为关于该生物体的基因组、生化网络和调控过程的信息的中央存储库。Pathway Tools软件是一个强大而全面的系统，用于构建生物体特异性数据库和基因组的途径分析。Pathway Tools使科学家社区能够创建，查询，可视化，分析MOD，并在Web上发布MOD。Pathway Tools支持构建联合收割机大量生物信息学数据库的MOD，包括基因组图谱、基因、操纵子、RNA、蛋白质、化合物、生化反应、代谢途径和调控相互作用。Pathway Tools是一个成熟的生产级软件环境，已被SRI以外的264个小组（见附录）用于分析1，969个基因组。 我们提出了重大改进的新途径工具模块，用于生产代谢通量模型的生物个体和微生物群落。该工具允许比类似工具更快地创建这些复杂模型。我们建议对Pathway Tools的Web界面进行重大重新设计。我们建议增强Pathway Tools网络代谢网络图和调控网络图，它们提供交互式的基于网络的细胞网络图。我们建议创建一个变更报告系统，用于通知科学家Pathway Tools数据库的更新。我们建议创建一个工具，用于推断多聚体蛋白质复合物的测序基因组，并扩展路径工具与几个序列相关的操作。我们建议为Pathway Tools的大型和不断增长的用户社区提供支持服务，维护软件的高质量文档，并每年创建两个经过彻底测试的软件版本。 公共卫生相关性：拟议的项目将产生软件工具，提高科学家利用基因组序列数据促进人类健康的能力。该软件能够创建中央数据库存储库和网站，这些数据库和网站包含致病细菌和实验模型生物（如实验室小鼠）的基因组数据和细胞网络数据。该软件允许研究人员使用直观的查询工具访问有关这些生物体的最新信息，并提供科学可视化功能，帮助科学家更快地了解大型复杂的数据集，并将这些数据应用于促进健康。

DESCRIPTION (provided by applicant): The completion of the genome sequence for an organism such as a disease-causing bacterium marks the start of a phase of accelerated research that can now lead to the production of a quantitative metabolic flux model for the organism. Such metabolic flux models have diverse applications. They enable basic scientific understanding of biochemical pathways. They allow computational predictions of which genes and reactions within the metabolic network are essential, thus facilitating the design of drugs against disease-causing bacteria. They support the engineering of new metabolic pathways, such as for bioenergy research. The huge quantity of data and knowledge defined by the genome sequence, and by the large number of past and future experimental findings for the organism, requires using a database as a central repository for information about the genome, the biochemical network, and the regulatory processes of that organism. The Pathway Tools software is a robust and comprehensive system for constructing organism-specific databases, and for pathway analysis of genomes. Pathway Tools enables communities of scientists to create, query, visualize, analyze MODs, and to publish the MODs on the web. Pathway Tools supports construction of MODs that combine a large number of bioinformatics datatypes, including genome maps, genes, operons, RNAs, proteins, chemical compounds, biochemical reactions, metabolic pathways, and regulatory interactions. Pathway Tools is a mature and production grade software environment that has been used by 264 groups outside SRI (see Appendix) to analyze 1,969 genomes. We propose major improvements to the new Pathway Tools module for producing metabolic flux models for individual organisms and for microbial communities. This tool allows much faster creation of these complex models than does comparable tools. We propose to perform a major redesign of the Pathway Tools web interfaces. We propose to enhance the Pathway Tools web metabolic network diagram and regulatory network diagram, which provide interactive, web-based cellular network maps. We propose to create a change-reporting system for notifying scientists of updates to Pathway Tools databases. We propose to create a tool for inferring multimeric protein complexes in sequenced genomes, and to extend Pathway Tools with several sequence-related operations. We propose to provide support services for the large and growing user community for Pathway Tools, to maintain quality documentation for the software, and to create two thoroughly tested releases of the software per year. PUBLIC HEALTH RELEVANCE: The proposed project will generate software tools that increase the ability of scientists to use genome sequence data to advance human health. This software enables creating central database repositories and websites con- training genome data and data on cellular networks for disease-causing bacteria, and for experimental model organisms such as the laboratory mouse. The software allows researchers to access the most up-to-date information about those organisms using intuitive querying tools, and provides scientific visualization capabilities that aid scientists in more quickly understanding large, complex collections of data, and applying that data to advance health.