Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.
Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.
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DOI：
10.1186/s13321-017-0219-x
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发表时间：
2017-05-25
影响因子：
8.6
通讯作者：
Fiehn O
中科院分区：
文献类型：
--
作者：
Blaženović I;Kind T;Torbašinović H;Obrenović S;Mehta SS;Tsugawa H;Wermuth T;Schauer N;Jahn M;Biedendieck R;Jahn D;Fiehn O
在基于质谱学的非靶向代谢组学中，很少有超过30%的化合物被鉴定出来。如果没有这些分子的真实身份，就不可能得出关于化合物的生物机制、途径关系和来源的结论。目前解决这种差异的唯一方法是在电子裂解软件中使用，通过比较从目标结构到实验串联质谱图(MS/MS)的理论MS/MS碎片并对其进行排序来识别未知化合物。我们比较了参与2016年CASMI挑战的四种公开可用的电子碎片算法(MetFragCL、CFM-ID、MAGMA+和MS-Finder)的性能。我们发现，优化元数据的使用、权重因子和组合不同工具的方式最终决定了每种方法的最终结果。我们综合分析了如何将不同工具的结果结合在一起，使用MAGMA+、CFM-ID和复合重要性信息以及MS/MS匹配，得出了训练数据的最终成功率为93%，挑战数据的最终成功率为87%。将MS/MS图谱与MS/MS文库进行匹配，在不使用任何In Silico工具的情况下，获得了60%的正确命中率，表明In Silico方法的使用仍然重要。本文的在线版本(doi：10.1186/s13321-0170219-x)包含补充材料，授权用户可以使用。
In mass spectrometry-based untargeted metabolomics, rarely more than 30% of the compounds are identified. Without the true identity of these molecules it is impossible to draw conclusions about the biological mechanisms, pathway relationships and provenance of compounds. The only way at present to address this discrepancy is to use in silico fragmentation software to identify unknown compounds by comparing and ranking theoretical MS/MS fragmentations from target structures to experimental tandem mass spectra (MS/MS). We compared the performance of four publicly available in silico fragmentation algorithms (MetFragCL, CFM-ID, MAGMa+ and MS-FINDER) that participated in the 2016 CASMI challenge. We found that optimizing the use of metadata, weighting factors and the manner of combining different tools eventually defined the ultimate outcomes of each method. We comprehensively analysed how outcomes of different tools could be combined and reached a final success rate of 93% for the training data, and 87% for the challenge data, using a combination of MAGMa+, CFM-ID and compound importance information along with MS/MS matching. Matching MS/MS spectra against the MS/MS libraries without using any in silico tool yielded 60% correct hits, showing that the use of in silico methods is still important. The online version of this article (doi:10.1186/s13321-017-0219-x) contains supplementary material, which is available to authorized users.