Construction and completion of flux balance models from pathway databases
Construction and completion of flux balance models from pathway databases
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DOI：
10.1093/bioinformatics/btr681
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发表时间：
2012-02-01
期刊：
影响因子：
5.8
通讯作者：
Karp, Peter D.
中科院分区：
文献类型：
--
作者：
Latendresse, Mario;Krummenacker, Markus;Karp, Peter D.
动机：通量平衡分析（FBA）是一种众所周知的基因组尺度代谢通量建模技术。通常情况下，FBA配方需要准确说明四组：生化反应、生物质代谢物、营养物质和分泌代谢物。FBA模型的开发既耗时又乏味，因为很难对这些集合进行完全准确的描述，也很难识别这些集合组成中的错误。例如，生物质中存在一种不可生产的代谢物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是模糊的，难以理解。结果：我们提出了一种基于混合整数线性规划（MILP）的多重间隙填充方法，以加速FBA模型的开发，该方法使用了名为MetaFlux的新工具。该方法建议对反应、生物量代谢物、营养物和分泌物进行修正。该方法直接从Pathway/Genome数据库中生成FBA模型。因此，在这个框架中开发的FBA模型可以很容易地使用Pathway Tools软件进行查询和可视化。通过在单个代谢途径的图表或代谢图上可视化预测的通量更容易理解。MetaFlux还可以去除冗余的高通量循环，一旦生成FBA模型就可以求解，并对基因敲除的影响进行建模。MetaFlux已通过构建大肠杆菌和智人的FBA模型得到验证。可用性：Pathway Tools with MetaFlux对学术用户免费提供，对商业用户收费。下载网址：biocyc.org/download.shtml。
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: biocyc.org/download.shtml.