Development and Support of the Pathway Tools Software

项目摘要 生物体基因组序列所定义的数据和知识的巨大广度和深度， 大量的其他实验发现的有机体，需要一个数据库（DB）作为中央存储库 获取有关该生物体的基因组、生化网络和调控过程的信息。的 Pathway Tools软件是一个强大而全面的系统，用于构建这种生物体特异性DB。路径- 工具使科学家社区能够创建、查询、可视化和分析生物数据库，并发布 这样的数据库在网络上。该软件支持构建生物数据库，联合收割机结合大量的生物素， 形成学数据库，包括基因组图谱、基因、操纵子、RNA、蛋白质、化合物、生物化学 反应、代谢途径和调节相互作用。Pathway Tools进一步实现了定性推理， 从测序的基因组进行代谢重建，并从 这些重建。这样的代谢模型能够计算预测哪些基因和反应 在代谢网络中的基因是必不可少的，从而促进了针对致病细菌的药物设计。 我们建议研究几种新的推理算法，为一个有序的 病原体基因组，以纳入Pathway Tools DB。一种算法可以检测交叉喂养和辅因子- 在生物群落内交换关系，以促进对人类的机械理解 微生物组第二种算法将使生物体的生化机制能够快速通信 基因组中的编码，例如在疾病爆发期间。第三种算法将改善预处理， 基于包括RNA-seq数据在内的新特征，在细菌基因组内对操纵子进行检测。我们亦建议 为Pathway Tools数据库实现一套基于云的编辑工具，这些工具在用户的Web中执行 浏览器.这些编辑工具将使科学家社区能够共同努力，更新和分享知识， 一个特定基因组的边缘。 Pathway Tools是一个成熟的生产级软件环境， 世界上有许可证，它已被引用1，650次。我们建议维护软件，例如安装 它的许多组件的新版本，并通过培训，文档和 bug修复。

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.