The application of Gaussian mixture models for signal quantification in MALDI-TOF mass spectrometry of peptides.
The application of Gaussian mixture models for signal quantification in MALDI-TOF mass spectrometry of peptides.
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DOI：
10.1371/journal.pone.0111016
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ramakrishnan V
中科院分区：
文献类型：
--
作者：
Spainhour JC;Janech MG;Schwacke JH;Velez JC;Ramakrishnan V
基质辅助激光解吸/电离飞行时间（MALDI-TOF）结合稳定同位素标准品（SIS）已被用于定量天然肽。这种通过MALDI-TOF方法进行的肽定量难以用重叠光谱中的离子电流定量含有肽的样品。在这些重叠的频谱中，电流相加在一起，这修改了峰高并使正常的SIS估计成问题。本文提出了一种基于已知物理常数的高斯混合模型来模拟已知化合物的同位素簇的方法。这种方法的特点是检查单一和重叠的化合物。将该方法与两种常用的单一化合物的SIS定量方法进行比较，即峰强度法和Riemann和曲线下面积（AUC）法。为了研究高斯混合方法的特征，使用血管紧张素II、血管紧张素-2-10和血管紧张素-1-9及其相关的SIS肽。结果表明，高斯混合法在估算单个化合物孤立同位素团簇的数量时具有与两种方法相似的特点。所有三种方法进行了测试，使用MALDI-TOF质谱收集的肽的肾素-血管紧张素系统。高斯混合法准确估计了几种分离的血管紧张素肽的天然与标记比率（比率估计误差为5.2%），估计误差与使用峰强度和Riemann和AUC方法计算的估计误差相似（分别为5.9%和7.7%）。对于重叠的血管紧张素肽（其他两种方法不适用），高斯混合物的估计误差为6.8%，在可接受范围内。总之，对于单一化合物，与现有的肽定量方法相比，高斯混合物方法是等效的或略微上级的，并且能够在可接受的误差范围内定量重叠（卷积）肽。
Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled with stable isotope standards (SIS) has been used to quantify native peptides. This peptide quantification by MALDI-TOF approach has difficulties quantifying samples containing peptides with ion currents in overlapping spectra. In these overlapping spectra the currents sum together, which modify the peak heights and make normal SIS estimation problematic. An approach using Gaussian mixtures based on known physical constants to model the isotopic cluster of a known compound is proposed here. The characteristics of this approach are examined for single and overlapping compounds. The approach is compared to two commonly used SIS quantification methods for single compound, namely Peak Intensity method and Riemann sum area under the curve (AUC) method. For studying the characteristics of the Gaussian mixture method, Angiotensin II, Angiotensin-2-10, and Angiotenisn-1-9 and their associated SIS peptides were used. The findings suggest, Gaussian mixture method has similar characteristics as the two methods compared for estimating the quantity of isolated isotopic clusters for single compounds. All three methods were tested using MALDI-TOF mass spectra collected for peptides of the renin-angiotensin system. The Gaussian mixture method accurately estimated the native to labeled ratio of several isolated angiotensin peptides (5.2% error in ratio estimation) with similar estimation errors to those calculated using peak intensity and Riemann sum AUC methods (5.9% and 7.7%, respectively). For overlapping angiotensin peptides, (where the other two methods are not applicable) the estimation error of the Gaussian mixture was 6.8%, which is within the acceptable range. In summary, for single compounds the Gaussian mixture method is equivalent or marginally superior compared to the existing methods of peptide quantification and is capable of quantifying overlapping (convolved) peptides within the acceptable margin of error.
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