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Construction and completion of flux balance models from pathway databases

机译:通过路径数据库构建和完成通量平衡模型

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摘要

>Motivation: Flux balance analysis (FBA) is a well-known technique for genome-scale modeling of metabolic flux. Typically, an FBA formulation requires the accurate specification of four sets: biochemical reactions, biomass metabolites, nutrients and secreted metabolites. The development of FBA models can be time consuming and tedious because of the difficulty in assembling completely accurate descriptions of these sets, and in identifying errors in the composition of these sets. For example, the presence of a single non-producible metabolite in the biomass will make the entire model infeasible. Other difficulties in FBA modeling are that model distributions, and predicted fluxes, can be cryptic and difficult to understand.>Results: We present a multiple gap-filling method to accelerate the development of FBA models using a new tool, called MetaFlux, based on mixed integer linear programming (MILP). The method suggests corrections to the sets of reactions, biomass metabolites, nutrients and secretions. The method generates FBA models directly from Pathway/Genome Databases. Thus, FBA models developed in this framework are easily queried and visualized using the Pathway Tools software. Predicted fluxes are more easily comprehended by visualizing them on diagrams of individual metabolic pathways or of metabolic maps. MetaFlux can also remove redundant high-flux loops, solve FBA models once they are generated and model the effects of gene knockouts. MetaFlux has been validated through construction of FBA models for Escherichia coli and Homo sapiens.>Availability: Pathway Tools with MetaFlux is freely available to academic users, and for a fee to commercial users. Download from: .>Contact: >Supplementary information: are available at Bioinformatics online.
机译:>动机:通量平衡分析(FBA)是一种用于代谢通量的基因组规模建模的众所周知的技术。通常,FBA制剂需要四组的准确规格:生化反应,生物质代谢产物,营养物质和分泌代谢产物。 FBA模型的开发可能非常耗时且乏味,因为难以对这些集合进行完全准确的描述,并且难以识别这些集合的组成中的错误。例如,生物质中单一不可生产的代谢产物的存在将使整个模型不可行。 FBA建模的其他困难是模型分布和预测通量可能难以理解。>结果:我们提出了一种多种填补空白的方法,以使用新工具加速FBA模型的开发,称为MetaFlux,基于混合整数线性规划(MILP)。该方法建议对反应,生物量代谢物,营养物质和分泌物进行校正。该方法直接从Pathway / Genome数据库生成FBA模型。因此,可以使用Pathway Tools软件轻松查询和可视化在此框架中开发的FBA模型。通过在单个代谢途径的图或代谢图上可视化预测的通量,可以更轻松地理解预测的通量。 MetaFlux还可以删除多余的高通量环,在生成FBA模型后对其进行求解,并对基因敲除的影响进行建模。 MetaFlux已通过构建用于大肠杆菌和智人的FBA模型进行了验证。>可用性:带有MetaFlux的路径工具可免费向学术用户免费提供,对商业用户则收费。下载地址:。>联系方式: >补充信息:可从Bioinformatics在线获得。

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