Isotopic peak intensity ratio based algorithm for determination of isotopic clusters and monoisotopic masses of polypeptides from high-resolution mass spectrometric data
Isotopic peak intensity ratio based algorithm for determination of isotopic clusters and monoisotopic masses of polypeptides from high-resolution mass spectrometric data
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DOI：
10.1021/ac800913b
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发表时间：
2008-10-01
影响因子：
7.4
通讯作者：
Lee, Sang-Won
中科院分区：
文献类型：
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作者：
Park, Kunsoo;Yoon, Joo Young;Lee, Sang-Won
确定同位素簇及其单一同位素质量是解释高分辨率质谱仪产生的复杂质谱的第一步。我们提出了一个数学模型的同位素分布的多肽和一个有效的解释算法。我们的模型使用两种类型的比率：同位素分布中两个相邻峰的强度比和三个相邻峰的强度比乘积。这些比率可以近似为多肽质量的简单函数，其值落在某些范围内，取决于多肽质量。给定一个光谱作为一个峰列表，我们的算法首先找到所有的同位素集群组成的两个或更多的峰。然后，它使用比率函数的范围对簇进行评分，并计算所识别的簇的单一同位素质量。我们的方法被施加到高分辨率质谱从傅里叶变换离子回旋共振（FTICR）质谱仪耦合到反相液相色谱（RPLC）。对于其氨基酸序列通过串联质谱（MS/MS）鉴定的多肽，我们应用基于THRASH的软件实现和我们的方法。我们的方法被观察到发现更多质量的已知肽时，由两种方法确定的总集群的数量是固定的。实验结果表明，我们的方法表现得更好的同位素质量集群的强度弱，同位素分布偏离其理论分布显着。此外，它正确地识别了一些基于THRASH的实现没有发现的同位素簇，特别是那些THRASH给出1 Da错配的同位素簇。我们的方法的另一个优点是它非常快，比计算最小二乘拟合的THRASH快得多。
Determining isotopic clusters and their monoisotopic masses is a first step in interpreting complex mass spectra generated by high-resolution mass spectrometers. We propose a mathematical model for isotopic distributions of polypeptides and an effective interpretation algorithm. Our model uses two types of ratios: intensity ratio of two adjacent peaks and intensity ratio product of three adjacent peaks in an isotopic distribution. These ratios can be approximated as simple functions of a polypeptide mass, the values of which fall within certain ranges, depending on the polypeptide mass. Given a spectrum as a peak list, our algorithm first finds all isotopic clusters consisting of two or more peaks. Then, it scores clusters using the ranges of ratio functions and computes the monoisotopic masses of the identified clusters. Our method was applied to high-resolution mass spectra obtained from a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer coupled to reverse-phase liquid chromatography (RPLC). For polypeptides whose amino acid sequences were identified by tandem mass spectrometry (MS/MS), we applied both THRASH-based software implementations and our method. Our method was observed to find more masses of known peptides when the numbers of the total clusters identified by both methods were fixed. Experimental results show that our method performed better for isotopic mass clusters of weak intensity where the isotopic distributions deviate significantly from their theoretical distributions. Also, it correctly identified some isotopic clusters that were not found by THRASH-based implementations, especially those for which THRASH gave 1 Da mismatches. Another advantage of our method is that it is very fast, much faster than THRASH that calculates the least-squares fit.