Advances in targeted proteomics and applications to biomedical research.
Advances in targeted proteomics and applications to biomedical research.
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DOI：
10.1002/pmic.201500449
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发表时间：
2016-08
期刊：
影响因子：
3.4
通讯作者：
Smith, Richard D.
中科院分区：
文献类型：
--
作者：
Shi, Tujin;Song, Ehwang;Nie, Song;Rodland, Karin D.;Liu, Tao;Qian, Wei-Jun;Smith, Richard D.
靶向蛋白质组学技术已成为系统生物学、生物医学研究和临床应用中强有力的蛋白质定量工具。最广泛使用的靶向蛋白质组学方法是选择性反应监测（SRM），也称为多反应监测（MRM），可用于细胞信号网络的量化和候选蛋白质生物标志物的临床前验证。作为我们之前对SRM灵敏度进展的综述的延伸，本文回顾了进一步提高SRM灵敏度的方法和技术的最新进展（从2012年至今），并强调了其在人体体液、组织和细胞系中的广泛生物医学应用。此外，我们还回顾了最近引入的两种靶向蛋白质组学方法，平行反应监测（PRM）和数据独立采集（DIA）与快速扫描高分辨率精确质量（HR/AM）仪器上的目标数据提取。这种监测所有目标产物离子的HR/AM靶向定量有效地解决了SRM在特异性和多路复用方面的局限性；而与SRM相比，PRM和DIA仍处于起步阶段，应用数量有限。因此，对于HR/AM靶向定量，我们将重点讨论方法开发，数据处理和分析，以及靶向蛋白质组学的优势和局限性。最后，对实现高灵敏度和高样品吞吐量的潜力，数百个目标蛋白的大规模定量的一般观点进行了讨论。
Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications in human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed.
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