QuickMod: A Tool for Open Modification Spectrum Library Searches
QuickMod: A Tool for Open Modification Spectrum Library Searches
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DOI：
10.1021/pr200152g
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Mueller, Markus
中科院分区：
文献类型：
--
作者：
Ahrne, Erik;Nikitin, Frederic;Mueller, Markus
与通过序列搜索工具建模的理论光谱相比，MS 2库光谱富含关于肽片段化模式的可再现信息。到目前为止，谱库搜索主要应用于检测库中存在的肽。然而，如果用大的前体质量窗口和适应的谱-谱匹配（SSM）评分算法进行搜索，则它们还允许发现文库肽的修饰变体。我们执行一个彻底的评估库光谱的使用，而不是理论肽光谱的识别PTM，分析光谱的一个很好的注释丰富的修改测试数据集编译从公共数据库。这些初步的研究激发了我们的修改容忍谱库搜索工具QuickMod的发展，该工具旨在识别谱库中列出的肽的修改变体，而无需用户估计样品中存在的修改的任何先前输入。我们在仔细测试了不同的SSM相似度得分后，构建了QuickMod的搜索算法。最后的频谱评分方案使用支持向量机（SVM）的评分功能的选择，以分类正确和不正确的SSM。在以给定的错误发现率（FDR）鉴定一系列修饰的肽之后，需要将修饰定位在肽序列上。我们提出了一种快速的修改站点分配算法，并评估其定位精度。最后，我们证明了QuickMod在速度和识别率方面与其他PTM分析软件解决方案相比表现良好。
MS2 library spectra are rich in reproducible information about peptide fragmentation patterns compared to theoretical spectra modeled by a sequence search tool. So far, spectrum library searches are mostly applied to detect peptides as they are present in the library. However, they also allow finding modified variants of the library peptides if the search is done with a large precursor mass window and an adapted Spectrum-Spectrum Match (SSM) scoring algorithm. We perform a thorough evaluation on the use of library spectra as opposed to theoretical peptide spectra for the identification of PTMs, analyzing spectra of a well annotated modification-rich test data set compiled from public data repositories. These initial studies motivate the development of our modification tolerant spectrum library search tool QuickMod, designed to identify modified variants of the peptides listed in the spectrum library without any prior input from the user estimating the modifications present in the sample. We built the search algorithm of QuickMod after carefully testing different SSM similarity scores. The final spectrum scoring scheme uses a support vector machine (SVM) on a selection of scoring features to classify correct and incorrect SSM. After identification of a list of modified peptides at a given False Discovery Rate (FDR), the modifications need to be positioned on the peptide sequence. We present a rapid modification site assignment algorithm and evaluate its positioning accuracy. Finally, we demonstrate that QuickMod performs favorably in terms of speed and identification rate when compared to other software solutions for PTM analysis.