title: Effects of Storage Time on Glycolysis in Donated Human Blood Units.
abstract: Background: 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;Study Design and Methods: 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;Results: 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;Conclusion: 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.
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA. zhen.qi@uky.edu.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Center for Transfusion and Cellular Therapy, Department of Pathology and Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. jroback@emory.edu.|Emory University Hospital, Blood Bank, Atlanta, GA 30322, USA. jroback@emory.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Roback
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA. eberhard.voit@bme.gatech.edu.
authors.forename: Eberhard O
authors.initials: EO
authors.lastname: Voit
keywords: blood storage; dynamic model; metabolomics; red blood cells; storage time effect; systems biology