Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay.

 
TitleReproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay.
Publication TypeJournal Article
Year of Publication2019
AuthorsTin, A, Yu, B, Ma, J, Masushita, K, Daya, N, Hoogeveen, RC, Ballantyne, CM, Couper, D, Rebholz, CM, Grams, ME, Alonso, A, Mosley, T, Heiss, G, Ganz, P, Selvin, E, Boerwinkle, E, Coresh, J
JournalJ Appl Lab Med
Volume4
Issue1
Pagination30-39
Date Published2019 07
ISSN2475-7241
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 -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 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 (

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.

DOI10.1373/jalm.2018.027086
Alternate JournalJ Appl Lab Med
PubMed ID31639705
PubMed Central IDPMC6814271
Grant ListHHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
R01 HL134320 / HL / NHLBI NIH HHS / United States
K01 DK107782 / DK / NIDDK NIH HHS / United States