Linear discriminant analysis-based estimation of the false discovery rate for phosphopeptide identifications
Linear discriminant analysis-based estimation of the false discovery rate for phosphopeptide identifications
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DOI：
10.1021/pr070510t
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Smith, Richard D.
中科院分区：
文献类型：
--
作者：
Du, Xiuxia;Yang, Feng;Smith, Richard D.
液相色谱-串联质谱（LC-MS/MS）联用技术的发展，使人们有可能在越来越大的规模和高通量的方式来表征磷酸肽。然而，从产生的大数据集中以类似的高通量方式提取置信的磷酸肽鉴定仍然很困难，严格估计一组磷酸肽鉴定的错误发现率（FDR）也是如此。本文描述了一个旨在解决这些问题的数据分析管道。第一步是重新分析磷酸肽鉴定，其中包含对所掺入的磷酸盐的模糊分配，以确定最可能的磷酸盐排列。下一步是采用期望最大化算法来估计肽得分的联合分布。然后进行线性判别分析以确定如何最佳地将联合收割机肽评分（在这种情况下，来自SEQUEST）组合成具有最大判别能力的判别评分。基于该判别分数，计算每个磷酸肽鉴定的p值和q值，然后估计磷酸肽鉴定FDR。这种数据分析方法被应用到数据的研究照射的人皮肤成纤维细胞，以提供一个强大的估计FDR的磷酸肽。Phosphopeptide FDR Estimate软件可从http://ncrr.pni.gov/software/免费下载。
The-development of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has made it possible to characterize phosphopeptides in an increasingly large-scale and high-throughput fashion. However, extracting confident phosphopeptide identifications from the resulting large data sets in a similar high-throughput fashion remains difficult, as does rigorously estimating the false discovery rate (FDR) of a set of phosphopeptide identifications. This article describes a data analysis pipeline designed to address these issues. The first step is to reanalyze phosphopeptide identifications that contain ambiguous assignments for the incorporated phosphate(s) to determine the most likely arrangement of the phosphate(s). The next step is to employ an expectation maximization algorithm to estimate the joint distribution of the peptide scores. A linear discriminant analysis is then performed to determine how to optimally combine peptide scores (in this case, from SEQUEST) into a discriminant score that possesses the maximum discriminating power. Based on this discriminant score, the p- and q-values for each phosphopeptide identification are calculated, and the phosphopeptide identification FDR is then estimated. This data analysis approach was applied to data from a study of irradiated human skin fibroblasts to provide a robust estimate of FDR for phosphopeptides. The Phosphopeptide FDR Estimator software is freely available for download at http://ncrr.pni.gov/software/.