De novo peptide sequencing by tandem MS using complementary CID and electron transfer dissociation
De novo peptide sequencing by tandem MS using complementary CID and electron transfer dissociation
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DOI：
10.1002/elps.200900332
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发表时间：
2009-11-01
期刊：
影响因子：
2.9
通讯作者：
Kohlbacher, Oliver
中科院分区：
文献类型：
--
作者：
Bertsch, Andreas;Leinenbach, Andreas;Kohlbacher, Oliver
由于肽前体离子的CID后通常获得的光谱中缺少碎片离子，因此使用串联MS对肽进行从头测序是困难的。在电子转移解离（ETD）后，用离子阱质谱仪中获得的光谱补充CID光谱显著增加了诊断离子的序列覆盖率。在这里提出的从头测序算法CompNovo中，将分而治之的方法与有效的质量分解算法相结合，以利用CID和ETD谱中包含的互补信息。在针对来自九种已知蛋白质的肽获得的定义明确的训练数据集优化算法参数后，将CompNovo算法应用于来自纤维堆囊菌细菌全蛋白提取物的肽的从头测序。对于该数据集中包含的2406对CID和ETD光谱，分配了675个完全正确的序列，其代表28.1%的成功率。结果表明，CompNovo算法与仅使用CID光谱或组合CID和ETD光谱的已发表方法相比，测序准确性得到显著提高
De novo sequencing of peptides using tandem MS is difficult due to missing fragment ions in the spectra commonly obtained after CID of peptide precursor ions. Complementing CID spectra with spectra obtained in an ion-trap mass spectrometer upon electron transfer dissociation (ETD) significantly increases the sequence coverage with diagnostic ions. in the de novo sequencing algorithm CompNovo presented here, a divide-and-conquer approach was combined with an efficient mass decomposition algorithm to exploit the complementary information contained in CID and ETD spectra. After optimizing the parameters for the algorithm on a well-defined training data set obtained for peptides from nine known proteins, the CompNovo algorithm was applied to the de novo sequencing of peptides derived from a whole protein extract of Sorangium cellulosum bacteria. To 2406 pairs of CID and ETD spectra contained in this data set, 675 fully correct sequences were assigned, which represent a success rate of 28.1%. It is shown that the CompNovo algorithm yields significantly improved sequencing accuracy as compared with published approaches using only CID spectra or combined CID and ETD spectra