An Isobaric Labeling Approach to Enhance Detection and Quantification of Tissue-Derived Plasma Proteins as Potential Early Disease Biomarkers.
An Isobaric Labeling Approach to Enhance Detection and Quantification of Tissue-Derived Plasma Proteins as Potential Early Disease Biomarkers.
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DOI：
10.3390/biom13020215
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发表时间：
2023-01-22
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
血浆的蛋白质组学分析对于推进精准医学和识别疾病的生物标志物具有很大的希望。然而，在血浆中循环的许多潜在生物标志物可能源自其他组织，并且仅以低丰度存在于血浆中。通过标准质谱方法准确检测和定量低丰度蛋白质仍然具有挑战性。此外，很难有把握地将低丰度血浆蛋白与其特定组织或器官来源联系起来。为了应对这些挑战，我们开发了一种基于使用串联质量标签（TMT）和组织参考样本的质谱方法。通过将这种方法应用于非人灵长类动物血浆样品，我们能够通过使用肾组织匀浆作为参考来鉴定和定量820种蛋白质。平均每个血浆样品鉴定出643 ± 16种蛋白质。在重复实验中鉴定的蛋白质中约有58%在两次都被鉴定。50 μg肾脏蛋白与10 μg血浆蛋白的比例，以及使用分子量最高（131）的TMT标记物作为肾脏参比品，在分析中产生了最大数量的蛋白质，并鉴定了血浆中主要存在于肾脏中的低丰度蛋白质。总的来说，这种方法有望有效地定量可能从特定组织释放的血浆蛋白，从而增加未来研究的推定疾病生物标志物的数量。
The proteomic analysis of plasma holds great promise to advance precision medicine and identify biomarkers of disease. However, it is likely that many potential biomarkers circulating in plasma originate from other tissues and are only present in low abundances in the plasma. Accurate detection and quantification of low abundance proteins by standard mass spectrometry approaches remain challenging. In addition, it is difficult to link low abundance plasma proteins back to their specific tissues or organs of origin with confidence. To address these challenges, we developed a mass spectrometry approach based on the use of tandem mass tags (TMT) and a tissue reference sample. By applying this approach to nonhuman primate plasma samples, we were able to identify and quantify 820 proteins by using a kidney tissue homogenate as reference. On average, 643 ± 16 proteins were identified per plasma sample. About 58% of proteins identified in replicate experiments were identified both times. A ratio of 50 μg kidney protein to 10 μg plasma protein, and the use of the TMT label with the highest molecular weight (131) for the kidney reference yielded the largest number of proteins in the analysis, and identified low abundance proteins in plasma that are prominently found in the kidney. Overall, this methodology promises efficient quantification of plasma proteins potentially released from specific tissues, thereby increasing the number of putative disease biomarkers for future study.
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影响因子：
4.6
作者：
Candia J;Cheung F;Kotliarov Y;Fantoni G;Sellers B;Griesman T;Huang J;Stuccio S;Zingone A;Ryan BM;Tsang JS;Biancotto A
通讯作者：
Biancotto A
影响因子：
64.5
作者：
Jiang L;Wang M;Lin S;Jian R;Li X;Chan J;Dong G;Fang H;Robinson AE;GTEx Consortium;Snyder MP
通讯作者：
Snyder MP
DOI：
10.1016/s0731-7085(00)00309-5
发表时间：
2000-08-15
影响因子：
3.4
作者：
Jemal, M;Ouyang, Z;Powell, ML
通讯作者：
Powell, ML
影响因子：
4.6
作者：
通讯作者：
--
影响因子：
5.5
作者：
Parker, Mark D.;Qin, Xue;Boron, Walter F.
通讯作者：
Boron, Walter F.