Aligning LC peaks by converting gradient retention times to retention index of peptides in proteomic experiments
Aligning LC peaks by converting gradient retention times to retention index of peptides in proteomic experiments
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DOI：
10.1093/bioinformatics/btn240
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发表时间：
2008-07-15
期刊：
影响因子：
5.8
通讯作者：
Ishihama, Yasushi
中科院分区：
文献类型：
--
作者：
Shinoda, Kosaku;Tomita, Masaru;Ishihama, Yasushi
动机：液相色谱-串联质谱（LC-MS/MS）是蛋白质组学研究中的有力工具，但是当肽保留信息用于鉴定目的时，比较多个LC-MS/MS运行或匹配观察到的和预测的保留时间仍然具有挑战性，因为LC条件的微小变化必然导致保留时间的变化。此外，与不同的LC-MS仪器或在不同的实验室获得的非连续保留数据必须对齐，以确认和利用迅速积累发表的蛋白质组学data.Results：我们已经开发出一种新的对齐方法肽保留时间线性溶剂强度（LSS）理论的基础上。我们发现LSS理论中的log k（0）（给定有机溶剂的保留因子的对数）可以用作肽的通用保留指数（RIP），其独立于LC梯度，并且仅取决于移动的相和固定相的组分。我们引入了一种基于机器学习的方案来优化梯度保留时间（t（g））到log k（0）的转换函数。使用优化的函数，可以在RIP标度上直接比较不同LC-MS系统获得的t（g）值。在拟南芥蛋白质组学数据的检查中，绝大多数保留时间变异性被去除，并且用各种LC-MS系统获得的五个数据集在RIP尺度上成功地对齐。
Motivation: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool in proteomics studies, but when peptide retention information is used for identification purposes, it remains challenging to compare multiple LC-MS/MS runs or to match observed and predicted retention times, because small changes of LC conditions unavoidably lead to variability in retention times. In addition, non-contiguous retention data obtained with different LC-MS instruments or in different laboratories must be aligned to confirm and utilize rapidly accumulating published proteomics data.Results: We have developed a new alignment method for peptide retention times based on linear solvent strength (LSS) theory. We found that log k(0) (logarithm of retention factor for a given organic solvent) in the LSS theory can be utilized as a universal retention index of peptides (RIP) that is independent of LC gradients, and depends solely on the constituents of the mobile phase and the stationary phases. We introduced a machine learning-based scheme to optimize the conversion function of gradient retention times (t(g)) to log k(0). Using the optimized function, t(g) values obtained with different LC-MS systems can be directly compared with each other on the RIP scale. In an examination of Arabidopsis proteomic data, the vast majority of retention time variability was removed, and five datasets obtained with various LC-MS systems were successfully aligned on the RIP scale.