The MetaCyc and BioCyc Pathway/Genome Databases [SRI Proposal ECU 10-626]

项目描述（由申请人提供）：项目目标是建立一个生物信息学基础，通过完整的基因组测序来破译每个生物体的代谢网络，以支持药物发现，代谢工程，系统生物学和基础科学。我们的方法是基于一个金标准的代谢数据库MetaCyc，它是由博士级生物学家从实验文献中策划的。第二个目标是进一步开发BioCyc，这是一个不断发展的途径/基因组数据库集合，可用于5,000-10,000个测序的原核生物基因组。BioCyc将成为原核生物基因组数据的首要来源，因为它计划全面覆盖原核生物基因组；多信息源的整合；其强大且用户友好的生物信息学搜索、可视化和分析工具；并通过多个访问通道分发数据。我们有四个具体目标。(1)扩展MetaCyc，一个高度管理的代谢途径和酶的多生物数据库，作为代谢信息的百科参考。MetaCyc可以用来预测生物体的代谢途径补体从其测序的基因组。有关实验确定的代谢途径和酶的信息将从生物医学文献中整理到MetaCyc中，重点是原核生物，真菌和植物信息。(2)通过计算生成BioCyc，这是一个生物特异性途径/基因组数据库的集合，用于完全测序的原核生物和模式生物，包括预测的代谢途径、预测的代谢途径孔填充物和预测的操纵子。(3)增强支持MetaCyc和BioCyc查询、可视化和分析的Pathway Tools软件，使其包含新的比较基因组学功能；包括基于基因组上下文的功能相关蛋白和新途径的预测；包括用于迭代浏览代谢物的反应邻域的工具；并提供针对多个BioCyc数据库的文本搜索。(4)通过门户网站和可下载的数据文件和软件向科学界提供MetaCyc和BioCyc。

DESCRIPTION (provided by applicant): The project objective is to develop a bioinformatics foundation for deciphering the metabolic network of every organism with a fully sequenced genome, in support of drug discovery, metabolic engineering, systems biology, and basic science. Our approach is based on a gold-standard metabolic database, MetaCyc, which is curated by Ph.D.- level biologists, from the experimental literature. A second objective is to further develop BioCyc, an evolving collection of Pathway/Genome Databases for 5,000-10,000 sequenced prokaryotic genomes. BioCyc will become the premier source of prokaryotic genome data because of its planned comprehensive coverage of prokaryotic genomes; its integration of multiple information sources; its powerful and user-friendly bioinformatics search, visualization, and analysis tools; and its distribution of data via multiple access channels. We have four specific aims. (1) To expand MetaCyc, a highly curated multi-organism database of metabolic pathways and enzymes that serves as an encyclopedic reference of metabolic information. MetaCyc can be used to predict the metabolic pathway complement of an organism from its sequenced genome. Information about experimentally determined metabolic pathways and enzymes will be curated into MetaCyc from the biomedical literature, with a focus on prokaryotic, fungal, and plant information. (2) To computationally generate BioCyc, a collection of organism-specific Pathway/Genome Databases for completely sequenced prokaryotes and model organisms that includes predicted metabolic pathways, predicted metabolic pathway hole fillers, and predicted operons. (3) To enhance the Pathway Tools software that supports the querying, visualization, and analysis of MetaCyc and BioCyc to include new comparative genomics capabilities; to include genome-context-based predic- tions of functionally related proteins and of novel pathways; to include a tool for iteratively browsing the reaction neighborhood of a metabolite; and to provide textual searches against multiple BioCyc databases. (4) To make MetaCyc and BioCyc available to the scientific community through a Web portal and via downloadable data files and software. PUBLIC HEALTH RELEVANCE: This project will create a powerful and user-friendly Web portal containing thousands of bacterial genomes, to- gether with the biochemical pathways encoded by each genome. By characterizing the metabolic pathways of thousands of organisms, this project will facilitate alterations to those pathways by metabolic engineering, such as to allow bacteria to synthesize drugs, and it will speed the development of drugs that kill disease-causing bacteria by enabling identification of essential metabolic pathways for disruption.