Plasma Protein Timings: Relative Contributions of Storage Time, Donor Age and Donation Season

Keywords: Biobank plasma variable storage time age season Development of the field of biorepository and biospecimen science has been shown to be a crucial tool for the development of biomarkers for health and disease and the development of testable hypotheses in clinical research (Vaught et al., 2011). The times when bio-specimens were tracked through laboratory notebooks and kept in a few freezers are over. Advances in epidemiology and omics science have led to a growth in national and international biobanks for regional healthy populations, or disease-specific populations of individuals to support large-scale research resources (Hallmans and Vaught, 2011). Specifically, the ease of processing blood derived plasma has favored the global spread of plasma biobanks. Plasma specimens lack the confounding factors associated with the cell release of proinflammatory cy-tokines and metabolites during clotting (Lee et al., 2015), which has resulted in plasma being preferred over serum for protein abundance analyses (Stenemo et al., 2016). Long-term stability of collected, stored plasma specimens is essential for longitudinal studies and for retrospective studies with specimens which have been for stored different periods. Large efforts have been made to collect carefully matched case and control cohorts, adjusting for non-disease related factors such as age and gender, or risk factors such as body mass index, weight and smoking. Also, plasma components have been found to change with storage time before separation and freezing, freezer storage time and number of freeze-thaw cycles (Paltiel et al., 2008; Harish et al., 2011). While donor individual age has been shown to affect the plasma protein levels in many studies (Liu et al., 2015), natural variables such as, time of day, weekday and general intra-individual variation which are also known to affect the variability and reproducibility of specimens stored in biobanks (Stenemo et al., 2016), have not been previously studied for their contribution to the variability in large cohorts of specimens from biobanks. From monozygotic and dizygotic twin studies, it has been demonstrated that the levels of different plasma proteins show vastly different patterns of abundance variability among humans, and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees (Liu et al., 2015). However, the compounded heterogenic nature of genetic and environmental variables as well as changes in the circadian/seasonal cycles of protein levels affecting human plasma specimens available in biobanks has not allowed, as yet, the determination of the specific weight of these parameters …