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阈限规避蛋白质组学分析流程。

Threshold-avoiding proteomics pipeline.

机构信息

IBM T. J. Watson Research Center, P.O. Box 218, Yorktown Heights, New York 10598, USA.

出版信息

Anal Chem. 2011 Oct 15;83(20):7786-94. doi: 10.1021/ac201332j. Epub 2011 Sep 22.

Abstract

We present a new proteomics analysis pipeline focused on maximizing the dynamic range of detected molecules in liquid chromatography-mass spectrometry (LC-MS) data and accurately quantifying low-abundance peaks to identify those with biological relevance. Although there has been much work to improve the quality of data derived from LC-MS instruments, the goal of this study was to extend the dynamic range of analyzed compounds by making full use of the information available within each data set and across multiple related chromatograms in an experiment. Our aim was to distinguish low-abundance signal peaks from noise by noting their coherent behavior across multiple data sets, and central to this is the need to delay the culling of noise peaks until the final peak-matching stage of the pipeline, when peaks from a single sample appear in the context of all others. The application of thresholds that might discard signal peaks early is thereby avoided, hence the name TAPP: threshold-avoiding proteomics pipeline. TAPP focuses on quantitative low-level processing of raw LC-MS data and includes novel preprocessing, peak detection, time alignment, and cluster-based matching. We demonstrate the performance of TAPP on biologically relevant sample data consisting of porcine cerebrospinal fluid spiked over a wide range of concentrations with horse heart cytochrome c.

摘要

我们提出了一个新的蛋白质组学分析流程,专注于最大限度地提高液相色谱-质谱(LC-MS)数据中检测到的分子的动态范围,并准确地定量低丰度峰,以识别具有生物学相关性的峰。尽管已经有很多工作致力于提高 LC-MS 仪器得出的数据质量,但本研究的目的是通过充分利用每个数据集内以及实验中多个相关色谱图中的信息来扩展分析化合物的动态范围。我们的目标是通过注意到它们在多个数据集之间的一致行为,将低丰度信号峰与噪声区分开来,而这一过程的核心是需要延迟剔除噪声峰,直到该流程的最终峰匹配阶段,即单个样本的峰出现在所有其他峰的背景下。这样就避免了应用可能过早剔除信号峰的阈值,因此该流程被命名为 TAPP:避免阈值的蛋白质组学分析流程。TAPP 专注于原始 LC-MS 数据的定量低水平处理,包括新颖的预处理、峰检测、时间对齐和基于聚类的匹配。我们在包含广泛浓度的马心细胞色素 c 猪脑脊髓液的生物相关样本数据上演示了 TAPP 的性能。

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