Spectral Library Generating Function for Assessing Spectrum-Spectrum Match Significance
Spectral Library Generating Function for Assessing Spectrum-Spectrum Match Significance
复制标题
用于评估谱-谱匹配显着性的谱库生成功能
DOI：
10.1007/978-3-642-37195-0_27
复制
发表时间：
2013
影响因子：
4.4
通讯作者：
N. Bandeira
中科院分区：
文献类型：
--
作者：
Mingxun Wang;N. Bandeira
串联质谱（MS/MS）仍然是复杂蛋白质组学样品高通量分析的首选技术。虽然MS/MS光谱通常通过与已知蛋白质序列的数据库匹配来识别，但光谱库搜索参考光谱集合的互补方法通过产生显著更多的识别光谱而始终优于基于序列的搜索。然而，虽然光谱库搜索受益于库光谱中记录的预期肽片段化模式的预先知识，但光谱-光谱匹配（SSM）的统计学显著性的估计继续受到难以找到“随机”SSM的适当定义以在估计真实SSM的显著性时用作空模型的阻碍。我们建议通过改变零假设来避免这个问题：不是确定在随机匹配的光谱之间观察到高SSM分数的概率，而是估计在相同分子的重复光谱之间观察到低SSM分数的概率。为此，我们明确建模的MS/MS峰强度的仪器测量的变化，并显示这些模型可以用来确定参考和查询光谱的同一分子之间的SSM分数的理论分布。虽然所提出的谱库生成函数（SLGF）方法可以用于计算任何加性SSM分数的理论分布（例如，任何点积），我们进一步展示了它如何用于计算参考和查询光谱之间的预期余弦分布。我们开发了一个光谱库搜索工具，Tremolo，并证明了这种基于SLGF的搜索工具显着优于当前最先进的光谱库搜索工具，并提供了一个详细的讨论背后的多种原因观察到的差异，在确定的MS/MS光谱集。
Tandem mass spectrometry (MS/MS) continues to be the technology of choice for high-throughput analysis of complex proteomics samples. While MS/MS spectra are commonly identified by matching against a database of known protein sequences, the complementary approach of spectral library searching against collections of reference spectra consistently outperforms sequence-based searches by resulting in significantly more identified spectra. However, while spectral library searches benefit from the advance knowledge of the expected peptide fragmentation patterns recorded in library spectra, estimation of the statistical significance of spectrum-spectrum matches (SSMs) continues to be hindered by difficulties in finding an appropriate definition of "random" SSMs to use as a null model when estimating the significance of true SSMs. We propose to avoid this problem by changing the null hypothesis: instead of determining the probability of observing a high SSM score between randomly matched spectra, we estimate the probability of observing a low SSM score between replicate spectra of the same molecule. To this end, we explicitly model the variation in instrument measurements of MS/MS peak intensities and show how these models can be used to determine a theoretical distribution of SSM scores between reference and query spectra of the same molecule. While the proposed spectral library generating function (SLGF) approach can be used to calculate theoretical distributions for any additive SSM score (e.g., any dot product), we further show how it can be used to calculate the distribution of expected cosines between reference and query spectra. We developed a spectral library search tool, Tremolo, and demonstrate that this SLGF-based search tool significantly outperforms current state-of-the-art spectral library search tools and provide a detailed discussion of the multiple reasons behind the observed differences in the sets of identified MS/MS spectra.
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影响因子：
4.4
作者：
Tabb, David L.;Vega-Montoto, Lorenzo;Rudnick, Paul A.;Variyath, Asokan Mulayath;Ham, Amy-Joan L.;Bunk, David M.;Kilpatrick, Lisa E.;Billheimer, Dean D.;Blackman, Ronald K.;Cardasis, Helene L.;Carr, Steven A.;Clauser, Karl R.;Jaffe, Jacob D.;Kowalski, Kevin A.;Neubert, Thomas A.;Regnier, Fred E.;Schilling, Birgit;Tegeler, Tony J.;Wang, Mu;Wang, Pei;Whiteaker, Jeffrey R.;Zimmerman, Lisa J.;Fisher, Susan J.;Gibson, Bradford W.;Kinsinger, Christopher R.;Mesri, Mehdi;Rodriguez, Henry;Stein, Stephen E.;Tempst, Paul;Paulovich, Amanda G.;Liebler, Daniel C.;Spiegelman, Cliff
通讯作者：
Spiegelman, Cliff
影响因子：
4.4
作者：
Rudomin EL;Carr SA;Jaffe JD
通讯作者：
Jaffe JD
影响因子：
7.4
作者：
Frewen, Barbara E.;Merrihew, Gennifer E.;MacCoss, Michael J.
通讯作者：
MacCoss, Michael J.
影响因子：
7.4
作者：
Venable, JD;Yates, JR
通讯作者：
Yates, JR