Evaluation of a large-scale aptamer proteomics platform among patients with kidney failure on dialysis.
Evaluation of a large-scale aptamer proteomics platform among patients with kidney failure on dialysis.
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DOI：
10.1371/journal.pone.0293945
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发表时间：
2023
期刊：
影响因子：
3.7
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中科院分区：
文献类型：
--
作者：
肾衰竭患者死亡率高，目前我们缺乏对这些患者进行危险分层的标志物。我们对测量约5000种蛋白质的改良适体测定法（SomaScan v.4.0）进行了质量控制研究，为在肾衰竭队列中使用该平台进行更大规模的研究做准备。从终末期肾病的心脏、内皮功能和动脉僵硬度（CERES研究）中选择了40名参与者，以分析2.5年随访期间死亡患者血浆中的技术和短期生物学变异性、正交相关性和差异蛋白表达。在慢性肾功能不全队列的421名参与者中研究了长期（1年）变异性。我们使用数据格式评估了4849种适体（4607种独特的蛋白质），包括原始数据和使用最大似然自适应归一化（ANML）格式化的数据，ANML是一种为肾功能正常个体的SomaScan数据开发的算法。在ANML格式中，中位[IQR]试验内变异系数（CV）为2.38%[1.76，3.40]，试验间CV为7.38%[4.61，13.12]。短期受试者内CV为5.76%[3.35，9.72];长期CV为8.71%[5.91，13.37]。适体与PTH、NT-proBNP、FGF-23和CRP的传统测定之间的斯皮尔曼相关性均> 0.7。在Bonferroni校正后，非存活者中蛋白质水平的倍数变化（FC）显著，包括SVEP 1（FC [95% CI] 2.14 [1.62，2.82]）、角膜蛋白聚糖（1.74 [1.40，2.15]）和LanC样蛋白1（0.56 [0.45，0.70]）。与原始适体数据相比，ANML格式数据中配对样品的技术和短期生物学变异性较低。ANML格式对与传统测定的正交相关性或蛋白质与死亡率表型的相关性的影响最小。SomaScan具有出色的技术变异性和低受试者内短期变异性。ANML格式可以促进生物标志物结果与利用该格式的其他研究的比较。我们希望SomaScan能为肾衰竭透析患者提供新的和可重复的信息。
Patients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure. Forty participants from the Cardiac, Endothelial Function and Arterial Stiffness in End-Stage Renal Disease (CERES study) were selected to analyze technical and short-term biological variability, orthogonal correlations and differential protein expression in plasma from patients who died during 2.5 year follow-up. Long-term (one year) variability was studied in 421 participants in the Chronic Renal Insufficiency Cohort. We evaluated 4849 aptamers (4607 unique proteins) using data formats including raw data and data formatted using Adaptive Normalization by Maximum Likelihood (ANML), an algorithm developed for SomaScan data in individuals with normal kidney function. In ANML format, median[IQR] intra-assay coefficient of variation (CV) was 2.38%[1.76, 3.40] and inter-assay CV was 7.38%[4.61, 13.12]. Short-term within-subject CV was 5.76% [3.35, 9.72]; long-term CV was 8.71%[5.91, 13.37]. Spearman correlations between aptamer and traditional assays for PTH, NT-proBNP, FGF-23 and CRP were all > 0.7. Fold-change (FC) in protein levels among non-survivors, significant after Bonferroni correction, included SVEP1 (FC[95% CI] 2.14 [1.62, 2.82]), keratocan (1.74 [1.40, 2.15]) and LanC-like protein 1 (0.56 [0.45, 0.70]). Compared to raw aptamer data, technical and short-term biological variability in paired samples was lower in ANML-formatted data. ANML formatting had minimal impact on orthogonal correlations with traditional assays or the associations of proteins with the phenotype of mortality. SomaScan had excellent technical variability and low within-subject short-term variability. ANML formatting could facilitate comparison of biomarker results with other studies that utilize this format. We expect SomaScan to provide novel and reproducible information in patients with kidney failure on dialysis.
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DOI：
10.1038/mtna.2014.49
发表时间：
2014-10-07
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
17.1
作者：
Jung IH;Elenbaas JS;Alisio A;Santana K;Young EP;Kang CJ;Kachroo P;Lavine KJ;Razani B;Mecham RP;Stitziel NO
通讯作者：
Stitziel NO
影响因子：
11.4
作者：
Cheriyan, Vino T.;Alfaidi, Mabruka;Nam, Hyung W.
通讯作者：
Nam, Hyung W.