Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona
Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona
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DOI：
10.1038/s41467-020-17033-7
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发表时间：
2020-07-22
影响因子：
16.6
通讯作者：
Farokhzad, Omid C.
中科院分区：
文献类型：
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作者：
Blume, John E.;Manning, William C.;Farokhzad, Omid C.
大规模、无偏倚的蛋白质组学研究受到血浆蛋白质组复杂性的限制。在这里，我们报告了一个高度并行的蛋白质定量平台，将纳米颗粒（NP）蛋白质冠与液相色谱-质谱联用技术相结合，以实现高效的蛋白质组学分析。蛋白质冠是在与生物流体接触时吸附到NP上的蛋白质层。改变工程化NP的物理化学性质转化为不同的蛋白质冠模式，从而能够对生物样品进行差异化和可再现的询问，包括对血浆蛋白质组进行深度采样。加标实验证实了线性信号响应。变异系数中位数为22%。我们筛选了43个NP，并选择了5个NP，它们在一项试点非小细胞肺癌分类研究中使用96孔自动化工作流程从141个血浆样本中检测到2,000多种蛋白质。我们简化的工作流程将覆盖深度和通量与精确定量相结合，基于蛋白质和NP之间的独特相互作用，专为深度和可扩展的定量蛋白质组学研究而设计。大规模、无偏见的生物样品（如血浆）蛋白质组学研究受到蛋白质组复杂性的限制。在本文中，作者开发了一个高度并行的蛋白质定量平台，利用多纳米颗粒蛋白质冠进行深度蛋白质组采样和生物标志物发现。
Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise quantification based on unique interactions between proteins and NPs engineered for deep and scalable quantitative proteomic studies. Large-scale, unbiased proteomics studies of biological samples like plasma are constrained by the complexity of the proteome. Herein, the authors develop a highly parallel protein quantitation platform leveraging multi nanoparticle protein coronas for deep proteome sampling and biomarker discovery.