Intensity-Independent Noise Filtering in FT MS and FT MS/MS Spectra for Shotgun Lipidomics
Intensity-Independent Noise Filtering in FT MS and FT MS/MS Spectra for Shotgun Lipidomics
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DOI：
10.1021/acs.analchem.7b00794
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发表时间：
2017-07-04
影响因子：
7.4
通讯作者：
Sheychenko, Andrej
中科院分区：
文献类型：
--
作者：
Schuhmann, Kai;Thomas, Henrik;Sheychenko, Andrej
鸟枪式脂质组学依赖于将总脂质提取物直接注入高分辨率串联质谱仪。一次散弹枪分析会产生几百个密集的。对FT MS和FT MS/MS谱图进行了分析，每个谱图可能包含数千个峰，尽管其中很小一部分属于脂质。通过调节最小峰强度阈值来消除噪声是有偏差的并且是低效的，因为脂质种类和类别在它们的天然丰度和电离能力方面变化。我们开发了一种在鸟枪式FT MS和FT MS/MS光谱中进行峰强度无关噪声过滤的方法，该方法利用了注入分析物的稳定组成，从而对其真实组分进行一致的时间无关检测。重复率过滤依赖于峰检测再现性的单一定量测量，而与其绝对强度、质量或假定的元素组成无关。在对比实验中，它去除了鸟枪光谱中95%以上的可检测信号，而不影响脂质鉴定和定量的准确性和范围。它还将光谱处理加速了15倍，同时处理的光谱数量增加了500倍，从而消除了高通量自下而上鸟枪脂质组学的主要瓶颈。
Shotgun lipidomics relies on the direct infusion of total lipid extracts into a high resolution tandem mass spectrometer. A single shotgun analysis produces several hundred of densely. opulated FT MS and FT MS/MS spectra, each of which might comprise thousands of peaks although a very small percentage of those belong to lipids. Eliminating noise by adjusting a minimal peak intensity threshold is biased and inefficient since lipid species and classes vary in their natural abundance and ionization capacity. We developed a method of peak intensity-independent noise filtering in shotgun FT MS and FT MS/MS spectra that capitalizes on a stable composition of the infused analyte leading to consistent time-independent detection of its bona fide components. Repetition rate filtering relies on a single quantitative measure of peaks detection reproducibility irrespectively of their absolute intensities, masses, or assumed elemental compositions. In comparative experiments, it removed more than 95% of signals detectable in shotgun spectra without compromising the accuracy and scope of lipid identification and quantification. It also accelerated spectra processing by 15-fold and increased the number of simultaneously processed spectra by similar to 500-fold hence eliminating the major bottleneck in high-throughput bottom-up shotgun lipidomics.