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Integration of relative metabolomics and transcriptomics time-course data in a metabolic model pinpoints effects of ribosome biogenesis defects on Arabidopsis thaliana metabolism
Scientific Reports ( IF 4.6 ) Pub Date : 2021-02-26 , DOI: 10.1038/s41598-021-84114-y
Christopher Pries 1 , Zahra Razaghi-Moghadam 2, 3 , Joachim Kopka 1 , Zoran Nikoloski 2, 3
Affiliation  

Ribosome biogenesis is tightly associated to plant metabolism due to the usage of ribosomes in the synthesis of proteins necessary to drive metabolic pathways. Given the central role of ribosome biogenesis in cell physiology, it is important to characterize the impact of different components involved in this process on plant metabolism. Double mutants of the Arabidopsis thaliana cytosolic 60S maturation factors REIL1 and REIL2 do not resume growth after shift to moderate 10 \(^{\circ }\hbox {C}\) chilling conditions. To gain mechanistic insights into the metabolic effects of this ribosome biogenesis defect on metabolism, we developed TC-iReMet2, a constraint-based modelling approach that integrates relative metabolomics and transcriptomics time-course data to predict differential fluxes on a genome-scale level. We employed TC-iReMet2 with metabolomics and transcriptomics data from the Arabidopsis Columbia 0 wild type and the reil1-1 reil2-1 double mutant before and after cold shift. We identified reactions and pathways that are highly altered in a mutant relative to the wild type. These pathways include the Calvin–Benson cycle, photorespiration, gluconeogenesis, and glycolysis. Our findings also indicated differential NAD(P)/NAD(P)H ratios after cold shift. TC-iReMet2 allows for mechanistic hypothesis generation and interpretation of system biology experiments related to metabolic fluxes on a genome-scale level.



中文翻译:

代谢模型中相关代谢组学和转录组学时间进程数据的整合确定核糖体生物发生缺陷对拟南芥代谢的影响

由于在驱动代谢途径所需的蛋白质合成中使用核糖体,因此核糖体生物发生与植物代谢密切相关。鉴于核糖体生物发生在细胞生理学中的核心作用,重要的是表征参与该过程的不同成分对植物代谢的影响。拟南芥胞质 60S 成熟因子REIL1REIL2 的双突变体在转移到中等 10 \(^{\circ }\hbox {C}\)后没有恢复生长 寒冷的条件。为了深入了解这种核糖体生物发生缺陷对代谢的代谢影响,我们开发了 TC-iReMet2,这是一种基于约束的建模方法,它整合了相关代谢组学和转录组学时间过程数据,以预测基因组规模水平的差异通量。我们使用了来自拟南芥哥伦比亚 0 野生型和reil1-1 reil2-1 的代谢组学和转录组学数据的 TC- iReMet2冷移前后双突变体。我们确定了突变体中相对于野生型发生高度改变的反应和途径。这些途径包括卡尔文-本森循环、光呼吸、糖异生和糖酵解。我们的研究结果还表明冷移后 NAD(P)/NAD(P)H 比率的差异。TC-iReMet2 允许在基因组水平上生成与代谢通量相关的系统生物学实验的机械假设和解释。

更新日期:2021-02-26
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