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，这一阶段现在可以导致产生生物体的定量代谢流量模型。这样的代谢流量模型有多种应用。它们使人们能够对生化途径有基本的科学理解。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。它们支持设计新的新陈代谢途径，例如用于生物能源研究。基因组序列定义的海量数据和知识，以及生物体过去和未来的大量实验发现，需要使用数据库作为关于基因组、生化网络和生物体调控过程的信息的中央储存库。Path Tools软件是一个强大而全面的系统，用于构建特定于生物体的数据库，并用于基因组的路径分析。路径工具使科学家社区能够创建、查询、可视化、分析MODS，并在网络上发布MODS。途径工具支持结合大量生物信息学数据类型的MODS的构建，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。Path Tools是一个成熟的生产级软件环境，已经被SRI以外的264个小组使用(见附录)来分析1,969个基因组。我们建议对新的路径工具模块进行重大改进，以生成单个生物体和微生物群落的代谢通量模型。与同类工具相比，该工具可以更快地创建这些复杂模型。我们建议对路径工具Web界面进行重大重新设计。我们建议增强路径工具网络代谢网络图和调节网络图，它们提供交互式的、基于网络的蜂窝网络地图。我们建议创建一个变更报告系统，以通知科学家Path Tools数据库的更新。我们建议创建一个工具来推断测序基因组中的多聚体蛋白质复合体，并使用几个与序列相关的操作来扩展路径工具。我们建议为不断增长的庞大的Path Tools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全面测试的软件版本。

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.