在动脉粥样硬化风险社区（ARIC）研究中比较不同平台的蛋白质组学测量。
Comparison of Proteomic Measurements Across Platforms in the Atherosclerosis Risk in Communities (ARIC) Study.
机构信息
Department of Epidemiology and Welch Center for Prevention, Epidemiology, & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA, USA.
Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
出版信息
Clin Chem. 2023 Jan 4;69(1):68-79. doi: 10.1093/clinchem/hvac186.
BACKGROUND
The plasma proteome can be quantified using different types of highly multiplexed technologies, including aptamer-based and proximity-extension immunoassay methods. There has been limited characterization of how these protein measurements correlate across platforms and with absolute measures from targeted immunoassays.
METHODS
We assessed the comparability of (a) highly multiplexed aptamer-based (SomaScan v4; Somalogic) and proximity-extension immunoassay (OLINK Proseek® v5003; Olink) methods in 427 Atherosclerosis Risk in Communities (ARIC) Study participants (Visit 5, 2011-2013), and (b) 18 of the SomaScan protein measurements against targeted immunoassays in 110 participants (55 cardiovascular disease cases, 55 controls). We calculated Spearman correlations (r) between the different measurements and compared associations with case-control status.
RESULTS
There were 417 protein comparisons (366 unique proteins) between the SomaScan and Olink platforms. The average correlation was r = 0.46 (range: -0.21 to 0.97; 79 [19%] with r ≥ 0.8). For the comparison of SomaScan and targeted immunoassays, 6 of 18 assays (growth differentiation factor 15 [GDF15], interleukin-1 receptor-like 1 [ST2], interstitial collagenase [MMP1], adiponectin, leptin, and resistin) had good correlations (r ≥ 0.8), 2 had modest correlations (0.5 ≤ r < 0.8; osteopontin and interleukin-6 [IL6]), and 10 were poorly correlated (r < 0.5; metalloproteinase inhibitor 1 [TIMP1], stromelysin-1 [MMP3], matrilysin [MMP7], C-C motif chemokine 2 [MCP1], interleukin-10 [IL10], vascular cell adhesion protein 1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], interleukin-18 [IL18], tumor necrosis factor [TNFα], and visfatin) overall. Correlations for SomaScan and targeted immunoassays were similar according to case status.
CONCLUSIONS
There is variation in the quantitative measurements for many proteins across aptamer-based and proximity-extension immunoassays (approximately 1/2 showing good or modest correlation and approximately 1/2 poor correlation) and also for correlations of these highly multiplexed technologies with targeted immunoassays. Design and interpretation of protein quantification studies should be informed by the variation across measurement techniques for each protein.
背景
可以使用不同类型的高度多重化技术来定量血浆蛋白质组，包括基于适配体和邻近延伸免疫测定方法。 这些蛋白质测量值在平台之间以及与靶向免疫测定的绝对测量值的相关性如何，其特征描述有限。
方法
我们评估了（a）在 427 名动脉粥样硬化风险社区（ARIC）研究参与者（访问 5，2011-2013 年）中高度多重化的基于适配体（SomaScan v4；Somalogic）和邻近延伸免疫测定（OLINK Proseek® v5003；Olink）方法之间的可比性，以及（b）在 110 名参与者（55 例心血管疾病病例，55 例对照）中，18 项 SomaScan 蛋白质测量值与靶向免疫测定的可比性。 我们计算了不同测量值之间的斯皮尔曼相关系数（r），并比较了与病例对照状态的关联。
结果
SomaScan 和 Olink 平台之间有 417 个蛋白质比较（366 个独特蛋白质）。 平均相关系数为 r = 0.46（范围：-0.21 至 0.97；79 [19%]的 r ≥ 0.8）。 在 SomaScan 和靶向免疫测定的比较中，6 种测定法（生长分化因子 15[GDF15]、白细胞介素 1 受体样 1[ST2]、间质胶原酶[MMP1]、脂联素、瘦素和抵抗素）具有良好的相关性（r ≥ 0.8），2 种具有适度相关性（0.5 ≤ r < 0.8；骨桥蛋白和白细胞介素 6[IL6]），而 10 种相关性较差（r < 0.5；基质金属蛋白酶抑制剂 1[TIMP1]、基质金属蛋白酶 1[MMP3]、基质金属蛋白酶 7[MMP7]、C 型趋化因子 2[MCP1]、白细胞介素 10[IL10]、血管细胞粘附蛋白 1[VCAM1]、细胞间粘附分子 1[ICAM1]、白细胞介素 18[IL18]、肿瘤坏死因子[TNFα]和内脏脂肪素）。 SomaScan 和靶向免疫测定的相关性根据病例状态相似。
结论
基于适配体和邻近延伸免疫测定的许多蛋白质的定量测量值存在差异（约 1/2 表现出良好或适度的相关性，约 1/2 相关性较差），并且这些高度多重化技术与靶向免疫测定的相关性也存在差异。 应该根据每种蛋白质的测量技术的差异来设计和解释蛋白质定量研究。
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