Software for Peak Finding and Elemental Composition Assignment for Glycosaminoglycan Tandem Mass Spectra
Software for Peak Finding and Elemental Composition Assignment for Glycosaminoglycan Tandem Mass Spectra
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DOI：
10.1074/mcp.ra118.000590
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发表时间：
2018-07-01
影响因子：
7
通讯作者：
Zaia, Joseph
中科院分区：
文献类型：
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作者：
Hogan, John D.;Klein, Joshua A.;Zaia, Joseph
糖胺聚糖（GAG）与蛋白聚糖（PG）共价连接，其特征在于重复的二糖单元和沿链沿着可变的硫酸化模式。GAG长度和硫酸化模式影响疾病病因、细胞信号传导和细胞的结构支持。我们和其他人已经证明了串联质谱法（MS 2）用于分配GAG结构的有用性;然而，手动解释串联质谱是耗时的，因此必须采用计算方法。在蛋白质组学领域，单一同位素峰和电荷状态的识别依赖于使用averagine或被分析的化合物类的平均构建块的算法。尽管这些方法对蛋白质和肽谱表现良好，但它们对GAG串联质谱表现不佳，因为单个平均结构单元不能表征GAG二糖单元的可变硫酸化。此外，有必要指定产物离子同位素模式以解释GAG的串联质谱。为了解决这些问题，我们开发了GAGfinder，这是第一个专门为GAG开发的串联质谱峰查找算法。我们将找峰定义为将实验同位素峰直接分配给给定的产物离子组成，而不是去卷积或峰拾取，这是更准确地描述先前提到的现有方法的术语。GAGfinder是一种有针对性的强力光谱分析方法，它使用前体成分信息来生成所有理论片段。GAGfinder还执行峰值同位素组成注释，这通常是基于平均值的方法的后续步骤。
Glycosaminoglycans (GAGs) covalently linked to proteoglycans (PGs) are characterized by repeating disaccharide units and variable sulfation patterns along the chain. GAG length and sulfation patterns impact disease etiology, cellular signaling, and structural support for cells. We and others have demonstrated the usefulness of tandem mass spectrometry (MS2) for assigning the structures of GAG saccharides; however, manual interpretation of tandem mass spectra is time-consuming, so computational methods must be employed. In the proteomics domain, the identification of monoisotopic peaks and charge states relies on algorithms that use averagine, or the average building block of the compound class being analyzed. Although these methods perform well for protein and peptide spectra, they perform poorly on GAG tandem mass spectra, because a single average building block does not characterize the variable sulfation of GAG disaccharide units. In addition, it is necessary to assign product ion isotope patterns to interpret the tandem mass spectra of GAG saccharides. To address these problems, we developed GAGfinder, the first tandem mass spectrum peak finding algorithm developed specifically for GAGs. We define peak finding as assigning experimental isotopic peaks directly to a given product ion composition, as opposed to deconvolution or peak picking, which are terms more accurately describing the existing methods previously mentioned. GAGfinder is a targeted, brute force approach to spectrum analysis that uses precursor composition information to generate all theoretical fragments. GAGfinder also performs peak isotope composition annotation, which is typically a subsequent step for averagine-based methods.