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

描述（由申请人提供）：该项目的目标是开发一个生物信息学基础，用于破译具有完全测序的基因组的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。我们的方法是基于黄金标准的代谢数据库，MetaCyc，这是由博士策划-水平的生物学家，从实验文献。第二个目标是进一步开发BioCyc，这是一个不断发展的5，000 - 10，000个测序原核基因组的途径/基因组数据库集合。BioCyc将成为原核基因组数据的首要来源，因为它计划全面覆盖原核基因组;它整合了多种信息源;它强大而用户友好的生物信息学搜索，可视化和分析工具;以及它通过多种访问渠道分发数据。 我们有四个具体目标。(1)为了扩展MetaCyc，一个高度策划的代谢途径和酶的多生物体数据库，作为代谢信息的植物参考。MetaCyc可用于从其测序的基因组预测生物体的代谢途径补体。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)为了计算生成BioCyc，生物体特异性途径/基因组数据库的集合，用于完全测序的原核生物和模型生物，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Pathway Tools软件（支持MetaCyc和BioCyc的查询、可视化和分析），以包括新的比较基因组学功能;包括功能相关蛋白质和新途径的基于基因组背景的预测;包括用于迭代浏览代谢物反应邻域的工具;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。 公共卫生相关性：该项目将创建一个功能强大且用户友好的门户网站，其中包含数千个细菌基因组，以及每个基因组编码的生化途径。通过表征数千种生物体的代谢途径，该项目将通过代谢工程促进对这些途径的改变，例如允许细菌合成药物，并通过识别破坏的基本代谢途径来加速药物的开发，从而杀死致病细菌。

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.