title: Progressive degradation of serum samples limits proteomic biomarker discovery.
abstract: Preanalytical variables play a key role in discovery of biomarkers. Although the effect of several preanalytical variables on the mass spectral profiles has been studied extensively, little is known about long-term storage of serum samples. This is important because samples used in case-control or epidemiological studies are usually stored for a long time before analysis. Here we evaluated long-term storage effects on mass spectral peak patterns of serum peptides extracted using weak cation exchange magnetic beads. For this, 20 serum samples stored at -80 degrees C were divided equally into two groups based on their storage time. We found that intensities of 26 mass spectral peaks significantly varied between these two groups. Intensities of these peaks significantly correlated with storage time. Genetic algorithm-based models generated using these 26 peaks could classify 63 additional samples into these two groups with 100% and 96% accuracy, respectively. We also show that storing samples for 10 months at -80 and -20 degrees C results in the appearance/disappearance or intensity variation of peaks, some of which were previously reported as disease biomarkers.
authors.affiliation: Department of Proteomics and Structural Biology, Institute of Genomics and Integrative Biology, New Delhi 110 007, India.
authors.forename: Shadab
authors.initials: S
authors.lastname: Ahmad
authors.forename: Elayanambi
authors.initials: E
authors.lastname: Sundaramoorthy
authors.forename: Reena
authors.initials: R
authors.lastname: Arora
authors.forename: Somdutta
authors.initials: S
authors.lastname: Sen
authors.forename: Ganesan
authors.initials: G
authors.lastname: Karthikeyan
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D005615:Freezing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D044967:Serum / Q000737:chemistry*; D013048:Specimen Handling; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D020543:Proteome