Spectra-first feature analysis in clinical proteomics - A case study in renal cancer
Spectra-first feature analysis in clinical proteomics - A case study in renal cancer
复制标题
临床蛋白质组学中的光谱优先特征分析 - 肾癌案例研究
DOI：
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
L. Wong
中科院分区：
文献类型：
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作者：
W. Goh;L. Wong
在蛋白质组学中，由于缺乏可靠的肽谱匹配，有用的信号可能无法观察到或丢失。选择差异光谱，然后进行关联肽/蛋白质图谱分析可能是提高分析灵敏度和全面性的补充策略（光谱优先范式）。这种方法是对标准方法的补充，在标准方法中，仅对由光谱中已识别的肽组装而成的最终蛋白质列表进行功能分析（蛋白质优先范例）。基于肾癌的案例研究，我们介绍了一种简单的光谱合并方法，MZ-bin。我们证明使用 MZ-bin 的差分光谱特征选择具有类别区分性，并且可以通过光谱关联映射追踪相关蛋白质。此外，以这种方式鉴定的蛋白质比直接从最终蛋白质列表中选择的蛋白质更具生物学一致性。对每种蛋白质的组成肽的分析揭示了高度的表达不一致，这表明测量的蛋白质表达实际上与真实蛋白质水平的近似值很差。此外，成分肽水平的分析可以提供对潜在生物学的更高分辨率的了解：通过MZ-bin，我们首次鉴定了已知肾癌标记物MAPT的差异剪接形式。我们的结论是，光谱优先分析范式是传统蛋白质优先分析范式的补充策略，可以提供更深层次的洞察。
In proteomics, useful signal may be unobserved or lost due to the lack of confident peptide-spectral matches. Selection of differential spectra, followed by associative peptide/protein mapping may be a complementary strategy for improving sensitivity and comprehensiveness of analysis (spectra-first paradigm). This approach is complementary to the standard approach where functional analysis is performed only on the finalized protein list assembled from identified peptides from the spectra (protein-first paradigm). Based on a case study of renal cancer, we introduce a simple spectra-binning approach, MZ-bin. We demonstrate that differential spectra feature selection using MZ-bin is class-discriminative and can trace relevant proteins via spectra associative mapping. Moreover, proteins identified in this manner are more biologically coherent than those selected directly from the finalized protein list. Analysis of constituent peptides per protein reveals high expression inconsistency, suggesting that the measured protein expressions are in fact, poor approximations of true protein levels. Moreover, analysis at the level of constituent peptides may provide higher resolution insight into the underlying biology: Via MZ-bin, we identified for the first time differential splice forms for the known renal cancer marker MAPT. We conclude that the spectra-first analysis paradigm is a complementary strategy to the traditional protein-first paradigm and can provide deeper level insight.
影响因子：
23.4
作者：
Brooks, Samira A.;Brannon, A. Rose;Parker, Joel S.;Fisher, Jennifer C.;Sen, Oishee;Kattan, Michael W.;Hakimi, A. Ari;Hsieh, James J.;Choueiri, Toni K.;Tamboli, Pheroze;Maranchie, Jodi K.;Hinds, Peter;Miller, C. Ryan;Nielsen, Matthew E.;Rathmell, W. Kimryn
通讯作者：
Rathmell, W. Kimryn