Department of Computer Science , Hanyang University , Seoul 04763 , South Korea.
Anal Chem. 2019 Sep 3;91(17):11324-11333. doi: 10.1021/acs.analchem.9b02445. Epub 2019 Aug 14.
Post-translational modifications regulate various cellular processes and are of great biological interest. Unrestrictive searches of mass spectrometry data enable the detection of any type of modification. Here we propose MODplus, which makes practical unrestrictive searches possible by allowing (1) hundreds of modifications, (2) multiple modifications per peptide, (3) the whole proteome database, and (4) any tolerant values in search parameters. The utility of MODplus was demonstrated in large human data sets of HEK293 cells and TMT-labeled phosphorylation enrichment. Notably, MODplus supports identifying different modification types at multiple sites and reports real chemical and biological modifications, as it has been very labor intensive to link unrestrictive search results to real modifications. We also confirmed the presence of () spectra that were not identifiable using targeted precursor masses. The MP spectra mostly resulted in identifications of wrong modifications and negatively affected the overall performance, often by as much as 10%. MODplus can rapidly recognize MP spectra and correct their identifications, resulting in increased identification rate up to 70% in the HEK293 data set as well as improved reliability.
翻译后修饰调节各种细胞过程，具有重大的生物学意义。对质谱数据进行无限制搜索能够检测任何类型的修饰。在此，我们提出了MODplus，它通过允许（1）数百种修饰、（2）每个肽段有多个修饰、（3）整个蛋白质组数据库以及（4）搜索参数中的任何宽容值，使得实际的无限制搜索成为可能。MODplus的实用性在人HEK293细胞的大型数据集以及TMT标记的磷酸化富集实验中得到了证明。值得注意的是，MODplus支持在多个位点识别不同的修饰类型，并报告真实的化学和生物学修饰，因为将无限制搜索结果与真实修饰联系起来一直非常耗费人力。我们还证实了存在一些无法使用靶向前体质量进行识别的（）光谱。这些MP光谱大多导致错误修饰的鉴定，并且通常会对整体性能产生负面影响，降幅高达10%。MODplus能够快速识别MP光谱并纠正其鉴定结果，在HEK293数据集中使鉴定率提高到70%，同时提高了可靠性。
