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- Title
Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay.
- Authors
Tin, Adrienne; Bing Yu; Jianzhong Ma; Kunihiro Masushita; Daya, Natalie; Hoogeveen, Ron C.; Ballantyne, Christie M.; Couper, David; Rebholz, Casey M.; Grams, Morgan E.; Alonso, Alvaro; Mosley, Thomas; Heiss, Gerardo; Ganz, Peter; Selvin, Elizabeth; Boerwinkle, Eric; Coresh, Josef
- Abstract
Background: There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized. Methods: We quantified 4001 plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4-9 weeks) and long-term (approximately 20 years) variability using paired t-tests with logtransformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR). Results: The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among 3693 protein analytes that passed quality control, half (n = 1846) had CVs < 5.0%, Spearman correlations > 0.89, and ICCs > 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P < 1.4 x 10-5, 681 increased, 185 decreased). PC1 had high correlations with age (-0.73) and eGFR (0.60). PC2 had moderate correlation with male sex (0.18) and white race (0.31). Conclusions: Multiplexed modified aptamer technology can assay thousands of proteins with excellent precision. Our results support the potential for large-scale studies of the plasma proteome over the lifespan.
- Subjects
APTAMERS; BLOOD proteins; GLOMERULAR filtration rate; ATHEROSCLEROSIS risk factors; MULTIPLE correspondence analysis (Statistics); RANK correlation (Statistics); INTRACLASS correlation
- Publication
Journal of Applied Laboratory Medicine, 2019, p30
- ISSN
2475-7241
- Publication type
Article
- DOI
10.1373/jalm.2018.027086