Targeted proteomic strategy for clinical biomarker discovery.
Targeted proteomic strategy for clinical biomarker discovery.
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临床生物标志物发现的靶向蛋白质组学策略。
DOI：
10.1016/j.molonc.2008.12.001
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发表时间：
2009-02
影响因子：
6.6
通讯作者：
Aebersold R
中科院分区：
文献类型：
--
作者：
Schiess R;Wollscheid B;Aebersold R
血浆蛋白质的高复杂性和大动态范围目前阻碍了足够大以可靠地检测疾病指示差异的疾病和对照血浆蛋白质组样品集的灵敏和高通量分析。为了规避这些技术限制，我们在这里描述了一种新的两阶段策略，用于质谱（MS）辅助发现、验证和确认疾病生物标志物。在最初的发现阶段，检测和鉴定在原代正常和患病组织中具有可区分的表达模式的N-连接糖蛋白。在第二步中，使用高灵敏度和特异性的选择反应监测（SRM）技术，对初始阶段鉴定的蛋白质进行血浆样品中的靶向MS分析。由于糖基化蛋白，如从细胞表面分泌或脱落的那些，可能驻留并持续存在于血液中，因此两阶段策略集中于血浆中组织来源的糖蛋白的定量。对N-糖蛋白组的关注不仅降低了分析物的复杂性，而且还针对与血浆中疾病的遥感相关的信息丰富的亚蛋白组。本文综述的基于N-糖蛋白的生物标志物发现和验证工作流程允许对蛋白候选组进行稳健鉴定，最终可以以可靠、非侵入性和定量的方式以高灵敏度在血浆中选择性监测。
The high complexity and large dynamic range of blood plasma proteins currently prohibits the sensitive and high throughput profiling of disease and control plasma proteome sample sets large enough to reliably detect disease indicating differences. To circumvent these technological limitations we describe here a new two stage strategy for the mass spectrometry (MS) assisted discovery, verification and validation of disease biomarkers. In an initial discovery phase N-linked glycoproteins with distinguishable expression patterns in primary normal and diseased tissue are detected and identified. In the second step the proteins identified in the initial phase are subjected to targeted MS analysis in plasma samples, using the highly sensitive and specific selected reaction monitoring (SRM) technology. Since glycosylated proteins, such as those secreted or shed from the cell surface are likely to reside and persist in blood, the two stage strategy is focused on the quantification of tissue derived glycoproteins in plasma. The focus on the N-glycoproteome not only reduces the complexity of the analytes, but also targets an information-rich subproteome which is relevant for remote sensing of diseases in the plasma. The N-glycoprotein based biomarker discovery and validation workflow reviewed here allows for the robust identification of protein candidate panels that can finally be selectively monitored in the blood plasma at high sensitivity in a reliable, non-invasive and quantitative fashion.
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影响因子：
7
作者：
Ishihama, Y;Oda, Y;Mann, M
通讯作者：
Mann, M
影响因子：
3.4
作者：
Deutsch, EW;Eng, JK;Aebersold, R
通讯作者：
Aebersold, R
影响因子：
2.9
作者：
BAYER, EA;BENHUR, H;WILCHEK, M
通讯作者：
WILCHEK, M
影响因子：
3.4
作者：
Echan, LA;Tang, HY;Speicher, DW
通讯作者：
Speicher, DW
影响因子：
46.9
作者：
Eriksson, Jan;Fenyo, David
通讯作者：
Fenyo, David