title: Biological variation of the platelet proteome in the elderly population and its implication for biomarker research.
abstract: Knowledge about the extent of total variation experienced between samples from different individuals is of great importance for the design of not only proteomics but every clinical study. This variation defines the smallest statistically significant detectable signal difference when comparing two groups of individuals. We isolated platelets from 20 healthy human volunteers aged 56-100 years because this age group is most commonly encountered in the clinics. We determined the technical and total variation experienced in a proteome analysis using two-dimensional DIGE with IPGs in the pI ranges 4-7 and 6-9. Only spots that were reproducibly detectable in at least 90% of all gels (n = 908) were included in the study. All spots had a similar technical variation with a median coefficient of variation (cv) of about 7%. In contrast, spots showed a more diverse total variation between individuals with a surprisingly low median cv of only 18%. Because most known biomarkers show an effect size in a 1-2-fold range of their cv, any future clinical proteomics study with platelets will require an analytical method that is able to detect such small quantitative differences. In addition, we calculated the minimal number of samples (sample size) needed to detect given protein expression differences with statistical significance.
authors.affiliation: Institute of Chemical Technologies and Analytics, Vienna University of Technology, A-1060 Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Winkler
authors.forename: Maria
authors.initials: M
authors.lastname: Zellner
authors.forename: Michael
authors.initials: M
authors.lastname: Diestinger
authors.forename: Rita
authors.initials: R
authors.lastname: Babeluk
authors.forename: Martina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Alexandra
authors.initials: A
authors.lastname: Goll
authors.forename: Sonja
authors.initials: S
authors.lastname: Zehetmayer
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Eduard
authors.initials: E
authors.lastname: Rappold
authors.forename: Ingrid
authors.initials: I
authors.lastname: Miller
authors.forename: Erich
authors.initials: E
authors.lastname: Roth
authors.forename: Günter
authors.initials: G
authors.lastname: Allmaier
authors.forename: Rudolf
authors.initials: R
authors.lastname: Oehler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000737:chemistry; D001792:Blood Platelets / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020543:Proteome / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D020543:Proteome