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

项目描述(申请人提供)：该项目的目标是建立一个生物信息学基础，用于破译具有全序列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。我们的方法是基于一个黄金标准的代谢数据库MetaCyc，该数据库由博士级别的生物学家从实验文献中挑选出来。第二个目标是进一步开发BioCyc，这是一个进化中的路径/基因组数据库集合，用于5,000-10,000个已测序的原核生物基因组。BioCyc将成为原核生物基因组数据的主要来源，因为它计划全面覆盖原核生物基因组；它整合了多种信息源；其强大和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)扩展MetaCyc，这是一个高度精选的代谢途径和酶的多生物数据库，作为代谢信息的百科全书参考。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，重点放在原核生物、真菌和植物信息上。(2)计算生成BioCyc，这是一个生物特有的途径/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、预测的代谢途径空洞填充物和预测的操纵子。(3)增强支持MetaCyc和BioCyc的查询、可视化和分析的Path Tools软件，以包括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质和新途径的预测；包括用于反复浏览代谢物的反应邻域的工具；以及提供对多个BioCyc数据库的文本搜索。(4)通过网络门户以及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.