Qi Zhen, Roback John D, Voit Eberhard O
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
Center for Transfusion and Cellular Therapy, Department of Pathology and Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA.
Metabolites. 2017 Mar 29;7(2):12. doi: 10.3390/metabo7020012.
: Donated blood is typically stored before transfusions. During storage, the metabolism of red blood cells changes, possibly causing storage lesions. The changes are storage time dependent and exhibit donor-specific variations. It is necessary to uncover and characterize the responsible molecular mechanisms accounting for such biochemical changes, qualitatively and quantitatively; : Based on the integration of metabolic time series data, kinetic models, and a stoichiometric model of the glycolytic pathway, a customized inference method was developed and used to quantify the dynamic changes in glycolytic fluxes during the storage of donated blood units. The method provides a proof of principle for the feasibility of inferences regarding flux characteristics from metabolomics data; : Several glycolytic reaction steps change substantially during storage time and vary among different fluxes and donors. The quantification of these storage time effects, which are possibly irreversible, allows for predictions of the transfusion outcome of individual blood units; : The improved mechanistic understanding of blood storage, obtained from this computational study, may aid the identification of blood units that age quickly or more slowly during storage, and may ultimately improve transfusion management in clinics.
捐献的血液通常在输血前储存。在储存过程中,红细胞的代谢会发生变化,可能导致储存损伤。这些变化取决于储存时间,并表现出供体特异性差异。有必要定性和定量地揭示和表征导致此类生化变化的相关分子机制。
基于代谢时间序列数据、动力学模型和糖酵解途径的化学计量模型的整合,开发了一种定制的推理方法,并用于量化献血单位储存期间糖酵解通量的动态变化。该方法为从代谢组学数据推断通量特征的可行性提供了原理证明。
在储存期间,几个糖酵解反应步骤会发生显著变化,并且在不同通量和供体之间存在差异。对这些可能不可逆的储存时间效应进行量化,有助于预测单个血液单位的输血结果。
从这项计算研究中获得的对血液储存的改进的机制理解,可能有助于识别在储存期间老化快或慢的血液单位,并最终改善临床输血管理。