Development and Support of the Pathway Tools Software

项目摘要 数据和知识的巨大广度和深度取决于一个有机体的基因组序列，以及由fi 生物体的大量其他实验性fi编码，需要一个数据库(DB)作为中央存储库 以获取有关基因组、生化网络和该生物体的调控过程的信息。这个 Path Tools软件是一个强大而全面的系统，用于构建这样的生物体物种fic DB。路径- Way Tools使科学家社区能够创建、查询、可视化和分析有机体数据库，并发布 网上有这样的数据库。该软件支持构建结合了大量生物素类的生物体数据库。 信息学数据类型，包括基因组图谱、基因、操纵子、RNA、蛋白质、化合物、生化 反应、代谢途径和调节相互作用。路径工具进一步使定性推理成为可能 从测序的基因组中重建代谢，并从基因组中创建定量代谢flUX模型 那些重建的东西。这样的新陈代谢模型能够计算预测哪些基因和反应 在代谢网络中是必不可少的，从而促进了针对致病细菌的药物的设计。 我们建议研究几种新的推理算法，以获得序列的新信息 病原体基因组包含在路径工具数据库中。一种算法将检测交叉喂养和辅因- 有机体群落内的交换关系，以促进对人类的机械性理解 微生物组。第二种算法将使生物体的生化机器能够快速通信 在它的基因组中编码给科学家，例如在疾病爆发期间。第三种算法将改进Pre-For 基于包括rna-seq数据在内的新特征对细菌基因组中操纵子的表述。我们还建议 为在用户Web内执行的路径工具数据库实施一套基于云的编辑工具 浏览器。这些编辑工具将使科学家社区能够共同更新和分享知识- 关于一个给定的基因组的边缘。 Path Tools是一个成熟的生产级软件环境，有10,800个研究小组 全世界都有许可证，它被引用了1650次。我们建议对软件进行维护，例如通过安装 许多组件的新版本，并通过培训、文档和 BugfiXing。

Project Summary The huge breadth and depth of data and knowledge defined by the genome sequence of an organism, and by large numbers of other experimental findings for the organism, requires a database (DB) 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 such organism-specific DBs. Path- way Tools enables communities of scientists to create, query, visualize, and analyze organism DBs, and to publish such DBs on the web. The software supports construction of organism DBs that combine a large number of bioin- formatics datatypes, including genome maps, genes, operons, RNAs, proteins, chemical compounds, biochemical reactions, metabolic pathways, and regulatory interactions. Pathway Tools further enables inference of qualitative metabolic reconstructions from sequenced genomes, and the creation of quantitative metabolic flux models from those reconstructions. Such metabolic models enable computational predictions of which genes and reactions within the metabolic network are essential, thus facilitating the design of drugs against disease-causing bacteria. We propose to research several new inference algorithms that derive new information for a sequenced pathogen genome for inclusion in Pathway Tools DBs. One algorithm will detect cross-feeding and cofactor- exchange relationships within a community of organisms to advance mechanistic understanding of the human microbiome. A second algorithm will enable rapid communication of the biochemical machinery of an organism encoded in its genome to scientists, such as during a disease outbreak. A third algorithm will improve the pre- diction of operons within bacterial genomes based on new features including RNA-seq data. We also propose to implement a suite of cloud-based editing tools for Pathway Tools databases that execute within the user's web browser. These editing tools will enable communities of scientists to work together to update and share knowl- edge about a given genome. Pathway Tools is a mature and production-grade software environment that 10,800 research groups around the world have licensed, and it has been cited 1,650 times. We propose to maintain the software, such as by installing new versions of its many components, and to support its user community through training, documentation, and bug fixing.