Machines learn phenotypes
Machines learn phenotypes
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机器学习表型
DOI：
10.1038/nmeth.2299
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发表时间：
2012
期刊：
影响因子：
48
通讯作者：
Natalie de Souza
中科院分区：
文献类型：
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作者：
Natalie de Souza
具有前所未有灵敏度的复合物可能有助于将这项技术带给更广泛的研究人员。观察这项技术是否能与先进的“自上而下”蛋白质组学方法（J.C. Tran等人，Nature 480,254 - 258, 2011）相结合将是一件特别有趣的事情，后者寻求在高通量下描述完整蛋白质及其翻译后修饰，从而在蛋白质组学规模上详细描述完整蛋白质复合物（P.D. Compton和N.L. Kelleher, Nat. Methods 9, 1065-1066, 2012）。Allison Doerr它们是如何工作的，但是当蛋白质被切割成多肽时，这些模式就很难解释了。此外，蛋白质很少单独起作用；相反，它们通过与细胞中的其他蛋白质和其他分子相互作用来进行生物过程。这种信息在典型的霰弹枪方法中也会丢失。但是，通过使用独特的质谱方法来检测和表征完整的蛋白质和蛋白质复合物，保留了提供蛋白质功能线索的宝贵信息。蛋白质被轻轻地电离到气相，从而保持了它们原有的三维结构；在适当的条件下，即使是大的、非共价结合的、可溶的和膜蛋白复合物也可以通过质谱法完整地观察到。然而，到目前为止，完整蛋白质复合物的质谱分析需要高度专业化的仪器，因此仅限于少数专家实验室。但是2012年的新发展（R.J. Rose et al., Nat. Methods 9,1084 - 1086, 2012），扩展了流行和强大的Orbitrap质量分析仪的使用，以检测大型完整蛋白质的完整蛋白质复合物的质谱仪
complexes with unprecedented sensitivity, may help bring the technology to a much broader swath of researchers. It will be particularly interesting to watch whether the technology can be merged with advanced ‘top down’ proteomics approaches (J.C. Tran et al., Nature 480, 254–258, 2011)—which seek to profile intact proteins and their post-translational modifications in high throughput—to allow detailed characterization of intact protein complexes on a proteome scale (P.D. Compton and N.L. Kelleher, Nat. Methods 9, 1065–1066, 2012). Allison Doerr how they function, but when the proteins are chopped up into peptides, these patterns become difficult to interpret. Further, proteins rarely act in isolation; rather, they carry out biological processes by interacting with other proteins and other molecules in the cell. Such information is also lost in a typical shotgun approach. But by using unique mass spectrometry methods to detect and characterize intact proteins and protein complexes, valuable information providing clues as to a protein’s function is retained. Proteins are gently ionized into the gas phase, which preserves their native three-dimensional structures; under the right conditions, even large, noncovalently bound, soluble and membrane-protein complexes can be observed intact by mass spectrometry. To date, however, mass spectrometry analysis of intact protein complexes has required highly specialized instrumentation and has therefore been limited to a handful of expert labs. But new developments in 2012 (R.J. Rose et al., Nat. Methods 9, 1084–1086, 2012), extending the use of the popular and powerful Orbitrap mass analyzer to detect large intact protein ❯❯Mass spectrometry of intact protein complexes