Crockford Derek J, Lindon John C, Cloarec Olivier, Plumb Robert S, Bruce Stephen J, Zirah Severine, Rainville Paul, Stumpf Chris L, Johnson Kelly, Holmes Elaine, Nicholson Jeremy K
Biological Chemistry, Division of Biomedical Sciences, Sir Alexander Fleming Building, Imperial College, London, SW7 2AZ, UK.
Anal Chem. 2006 Jul 1;78(13):4398-408. doi: 10.1021/ac060168o.
A new analytical strategy for biomarker recovery from directly coupled ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC Tof MS) data on biofluids is presented and exemplified using a study on hydrazine-induced liver toxicity. A key step in the strategy involves a novel procedure for reducing the spectroscopic search space by differential analysis of cohorts of normal and pathological samples using an orthogonal projection to latent structures discriminant analysis (O-PLS-DA). This efficiently sorts principal discriminators of toxicity from the background of thousands of metabolic features commonly observed in data sets generated by UPLC-MS analysis of biological fluids and is thus a powerful tool for biomarker discovery.
本文提出了一种从生物流体的直接耦合超高效液相色谱飞行时间质谱（UPLC Tof MS）数据中恢复生物标志物的新分析策略，并通过一项关于肼诱导肝毒性的研究进行了举例说明。该策略的一个关键步骤涉及一种新颖的程序，即使用正交投影到潜在结构判别分析（O-PLS-DA）对正常和病理样本队列进行差异分析，以减少光谱搜索空间。这有效地从生物流体UPLC-MS分析生成的数据集中通常观察到的数千个代谢特征的背景中筛选出毒性的主要判别因素，因此是生物标志物发现的有力工具。
