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Fast reconstruction of compact context-specific metabolic networks via integration of microarray data

机译:快速重建紧凑的上下文特定代谢网络   微阵列数据的整合

摘要

Recently we proposed an algorithm for the fast reconstruction of compactcontext-specific metabolic networks (FASTCORE) that allowed dropping thereconstruction time to the time order of seconds (Vlassis et al.,2014). Thisextremely low computational demand opens new possibilities for improving thequality of the models. Several rounds of model reconstruction, testing of themodel's predictions against real experimental data, curation steps of the inputmodel and the set of core reactions as well as cross-validations assays arerequired to reconstruct high-quality models. These semi-automated modelcurations steps are in such extend not possible with competing algorithms dueto their high computational demands. To adapt FASTCORE for the integration ofmicroarray data, we therefore propose a new workflow: FASTCORMICS. FASTCORMICSrequires as input microarray data and a Genome-scale reconstruction.FASTCORMICS is devoid of heuristic parameter settings and has a lowcomputational demand with overall building times in the order of a few minutes.FASTCORMICS preprocesses the microarrays data with the discretization toolBarcode (Zillox et al, 2007). Barcode uses prior knowledge on the intensitydistribution of each probe set for a given microarray platform to segregatebetween expressed genes and non-expressed genes. This preprocessing step allowscircumventing the need of setting a heuristic expression threshold, which iscritical for the output models as in response to this threshold alternativepathways or subsystems might be included or excluded, thereby heavily changingthe functionalities of the model. In general, FASTCORMICS outperforms competing algorithms and allows obtaininghigh-quality, robust models in a high-throughput manner. This will allow theuse of metabolic modelling as routine process for the analysis of microarraydata e.g. in the field of personalized medicine.
机译:最近,我们提出了一种用于快速重建紧凑上下文特定代谢网络(FASTCORE)的算法,该算法允许将构建时间减少到几秒钟的时间顺序(Vlassis等,2014)。这种极低的计算需求为改善模型的质量开辟了新的可能性。需要几轮模型重建,针对真实实验数据的模型预测测试,输入模型的管理步骤以及一组核心反应以及交叉验证分析,才能重建高质量的模型。由于竞争算法的高计算需求,这些半自动化模型处理步骤无法用竞争算法进行扩展。为了使FASTCORE适应微阵列数据的整合,我们提出了一个新的工作流程:FASTCORMICS。 FASTCORMICS需要输入微阵列数据并进行基因组规模的重建.FASTCORMICS缺乏启发式参数设置,对计算的需求较低,总构建时间约为几分钟.FASTCORMICS使用离散化工具Barcode预处理微阵列数据(Zillox等, 2007)。条形码使用关于给定微阵列平台的每个探针集的强度分布的先验知识,以分离表达的基因和未表达的基因之间。该预处理步骤允许避免设置启发式表达阈值的需求,这对于输出模型至关重要,因为响应于该阈值,可能包括或排除了替代路径或子系统,从而极大地改变了模型的功能。通常,FASTCORMICS优于竞争对手的算法,并可以以高通量的方式获得高质量,强大的模型。这将允许使用代谢模型作为分析微阵列数据的常规方法,例如在个性化医学领域。

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  • 年度 2014
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  • 正文语种 {"code":"en","name":"English","id":9}
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