TY - JOUR
T1 - Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay
AU - Tin, Adrienne
AU - Yu, Bing
AU - Ma, Jianzhong
AU - Masushita, Kunihiro
AU - Daya, Natalie
AU - Hoogeveen, Ron C.
AU - Ballantyne, Christie M.
AU - Couper, David
AU - Rebholz, Casey M.
AU - Grams, Morgan E.
AU - Alonso, Alvaro
AU - Mosley, Thomas
AU - Heiss, Gerardo
AU - Ganz, Peter
AU - Selvin, Elizabeth
AU - Boerwinkle, Eric
AU - Coresh, Josef
N1 - Publisher Copyright:
© 2018 American Association for Clinical Chemistry.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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 log-transformed 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 × 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.
AB - 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 log-transformed 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 × 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.
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U2 - 10.1373/jalm.2018.027086
DO - 10.1373/jalm.2018.027086
M3 - Article
C2 - 31639705
AN - SCOPUS:85083454352
SN - 2576-9456
VL - 4
SP - 30
EP - 39
JO - Journal of Applied Laboratory Medicine
JF - Journal of Applied Laboratory Medicine
IS - 1
ER -