Improving safety and efficacy of platelet pathogen inactivation techniques through systems biology

Project Summary Platelet transfusion is critical for severely bleedingfunctionally abnormal plateletsor low platelet counts due to oncology medicationsand nearlymillion units are transfused in the United States and Europe annuallyIn the United Statesplatelets can only be stored fordays due to concerns over contamination with pathogenic organismsThis results in waste ofof the platelet supply in the USNew photochemical methods have been developed for pathogen inactivationhowever they may adversely affect the platelet quality and thus transfusion efficacyPlatelet additive solutions have the possibility to prevent and reverse this loss of quality and improve the efficacy of pathogen inactivation techniquesWhile the benefits are well knownthere has been little progress in developing new platelet additive solutions for increasing quality and safety of platelet transfusion because there is a lack of broad understanding of the biochemical decline following pathogen inactivation techniquesWe have developed computational tools that utilize high throughput metabolite profiling data to gain a global understanding of platelet metabolic declineThe proposed program will generate time course globalquantitative metabolite profiling to track intracellular and extracellular platelet metabolites following pathogen inactivationWe will apply our recently developed computational platform to this data to fully interpret and analyze platelet metabolite profiles following pathogen inactivation techniquesThis robust platform utilizes statistical analysissystems biology of metabolic networksand data driven models to gain a deep biochemical understanding that will be employed to quantitatively predict optimal additive solutions to alleviate pathogen inactivation techniquesEach predicted solution will be evaluated based on biological efficacycostand regulatory hurdlesPredicted additives will be chosen for experimental validation and testing in Phase II Project Narrative Platelet transfusion units can only be stored for five days in the United States due to concerns over contamination with pathogenic organismsNew technologies have emerged to pathogen inactivate platelet unitshowever the technique may adversely affect platelet qualityAs part of this proposalnovel computational methods will be developed and applied to comprehensively understand the degradation of platelets after pathogen inactivation and to predict new additive solutions that prevent or revert degradation thus increasing platelet transfusion quality and extending shelf life