Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore.
Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore.
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DOI：
10.1021/acs.jproteome.5b01098
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发表时间：
2016-08-05
影响因子：
4.4
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Kou Q;Zhu B;Wu S;Ansong C;Tolić N;Paša-Tolić L;Liu X
由于一级结构改变（PSA）如遗传变异、选择性剪接和翻译后修饰（PTM），可以从单个基因产生各种蛋白质型。自上而下的质谱法能够分析完整的蛋白质和识别多种PSA的模式，使其成为研究复杂蛋白质型的首选方法。在自上而下的蛋白质组学中，蛋白质型鉴定通常通过针对蛋白质序列数据库搜索串联质谱来进行，所述蛋白质序列数据库仅包含蛋白质组中每个基因或转录物变体的一个参考蛋白质序列。由于蛋白质数据库的不完整性，与参考序列相比，鉴定的蛋白质型可能含有未知的PSA。蛋白质型表征是识别和定位蛋白质型中的PSA。尽管已经提出了许多软件工具用于通过自上而下质谱法进行蛋白质型鉴定，但在鉴定的蛋白质型-谱-匹配中的蛋白质型的表征仍然主要依赖于手动注释。我们建议使用的修改识别分数（MIScore），这是基于贝叶斯模型，自动识别和定位PTMs的proteoforms。实验表明，MIScore在识别和定位一个或两个修改时是准确的。
Various proteoforms may be generated from a single gene due to primary structure alterations (PSAs) such as genetic variations, alternative splicing, and post-translational modifications (PTMs). Top-down mass spectrometry is capable of analyzing intact proteins and identifying patterns of multiple PSAs, making it the method of choice for studying complex proteoforms. In top-down proteomics, proteoform identification is often performed by searching tandem mass spectra against a protein sequence database that contains only one reference protein sequence for each gene or transcript variant in a proteome. Because of the incompleteness of the protein database, an identified proteoform may contain unknown PSAs compared with the reference sequence. Proteoform characterization is to identify and localize PSAs in a proteoform. Although many software tools have been proposed for proteoform identification by top-down mass spectrometry, the characterization of proteoforms in identified proteoform-spectrum-matches still relies mainly on manual annotation. We propose to use the Modification Identification Score (MIScore), which is based on Bayesian models, to automatically identify and localize PTMs in proteoforms. Experiments showed that the MIScore is accurate in identifying and localizing one or two modifications.