Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease.
Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease.
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致力于诊断和治疗人类疾病的综合和定量蛋白质组学。
DOI：
10.1002/pmic.201600079
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发表时间：
2017-01
期刊：
影响因子：
3.4
通讯作者：
Kentsis A
中科院分区：
文献类型：
--
作者：
Cifani P;Kentsis A
质谱蛋白质组学具有上级分析功能，非常适合于人类疾病的基础研究和临床诊断。现代质谱技术能够对致病生物化学过程进行详细的功能表征，这是通过准确和全面地定量蛋白质及其调节化学修饰实现的。在这里，我们描述了如何利用高精度质谱结合高分辨率色谱分离，以满足这些分析要求的机制为重点的方式。我们回顾能够产生准确的测量蛋白质丰度和翻译后修饰化学计量的定量方法。然后，我们讨论了如何利用实验设计和色谱分辨率来实现复杂生物蛋白质组中生化过程的全面功能表征。最后，我们描述了目前的一个共同的功能蛋白质修饰：可逆磷酸化的定量分析方法。总之，目前高分辨率色谱和质谱蛋白质组学的仪器和方法准备立即转化为改进的儿科和成人疾病的诊断策略。
Given superior analytical features, mass spectrometry proteomics is well suited for the basic investigation and clinical diagnosis of human disease. Modern mass spectrometry enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy mass spectrometry in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner. We review the quantification methods capable of producing accurate measurements of protein abundance and post-translational modification stoichiometries. We then discuss how experimental design and chromatographic resolution can be leveraged to achieve comprehensive functional characterization of biochemical processes in complex biological proteomes. Finally, we describe current approaches for quantitative analysis of a common functional protein modification: reversible phosphorylation. In all, current instrumentation and methods of high-resolution chromatography and mass spectrometry proteomics are poised for immediate translation into improved diagnostic strategies for pediatric and adult diseases.