The MetaCyc and BioCyc Pathway/Genome Databases

描述（由申请人提供）：长期目标是开发生物信息学基础，用于破译具有完全测序基因组的每个生物体的代谢网络，以支持药物发现，代谢工程和系统生物学。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，严格来自实验文献。MetaCyc中的知识通过自动创建数百个生物体特异性途径/基因组数据库而在计算上扩展到其他生物体。我们的具体目标是（1）扩展MetaCyc，一个高度策划的多生物体代谢途径和酶数据库，作为代谢信息的植物学参考。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，重点关注微生物和植物途径和酶。(2)计算生成BioCyc，这是所有完全测序的微生物的生物体特异性途径/基因组数据库的集合，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，包括新的途径预测算法、改进的网站和管理1000个基因组的可扩展性。(4)使MetaCyc和BioCyc以多种格式提供。BioCyc数据库将使用先进且经过仔细验证的算法通过计算管道生成。MetaCyc和BioCyc数据将使用途径编辑软件在丰富的数据库模式中捕获，并通过多种访问机制公开提供，包括用户友好的网站和BioPAX标准途径格式。代谢途径构成生命系统的生化基础。通过快速表征数百种微生物的代谢途径，该项目将促进代谢工程师改变这些途径，例如允许细菌合成药物。它将加速药物的开发，通过识别破坏的基本代谢途径来杀死致病细菌。

DESCRIPTION (provided by applicant): The long-term 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, and systems biology. Our approach is based on a gold-standard metabolic database, MetaCyc, which is curated by Ph.D.-level biologists, strictly from the experimental literature. The knowledge in MetaCyc is extended computationally to other organisms by the automated creation of hundreds of organism-specific pathway/genome databases. Our specific aims are (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 microbial and plant pathways and enzymes. (2) To computationally generate BioCyc, a collection of organism-specific pathway/genome databases for all completely sequenced microbes 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 a new pathway prediction algorithm, an improved Web site, and scalability to manage 1000 genomes. (4) To make MetaCyc and BioCyc available in several formats. The BioCyc databases will be generated through a computational pipeline using advanced and carefully validated algorithms. MetaCyc and BioCyc data will be captured within a rich database schema using pathway editing software, and made publicly available through multiple access mechanisms, including a user-friendly Web site and the BioPAX standard pathway format. Metabolic pathways form the biochemical foundation of living systems. By quickly characterizing the metabolic pathways of hundreds of microbes, this project will facilitate alterations to those pathways by metabolic engineers, such as to allow bacteria to synthesize drugs. It will speed the development of drugs that kill disease-causing bacteria by enabling identification of essential metabolic pathways for disruption.