Kusebauch Ulrike, Campbell David S, Deutsch Eric W, Chu Caroline S, Spicer Douglas A, Brusniak Mi-Youn, Slagel Joseph, Sun Zhi, Stevens Jeffrey, Grimes Barbara, Shteynberg David, Hoopmann Michael R, Blattmann Peter, Ratushny Alexander V, Rinner Oliver, Picotti Paola, Carapito Christine, Huang Chung-Ying, Kapousouz Meghan, Lam Henry, Tran Tommy, Demir Emek, Aitchison John D, Sander Chris, Hood Leroy, Aebersold Ruedi, Moritz Robert L
Institute for Systems Biology, Seattle, WA 98109, USA.
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
Cell. 2016 Jul 28;166(3):766-778. doi: 10.1016/j.cell.2016.06.041. Epub 2016 Jul 21.
The ability to reliably and reproducibly measure any protein of the human proteome in any tissue or cell type would be transformative for understanding systems-level properties as well as specific pathways in physiology and disease. Here, we describe the generation and verification of a compendium of highly specific assays that enable quantification of 99.7% of the 20,277 annotated human proteins by the widely accessible, sensitive, and robust targeted mass spectrometric method selected reaction monitoring, SRM. This human SRMAtlas provides definitive coordinates that conclusively identify the respective peptide in biological samples. We report data on 166,174 proteotypic peptides providing multiple, independent assays to quantify any human protein and numerous spliced variants, non-synonymous mutations, and post-translational modifications. The data are freely accessible as a resource at http://www.srmatlas.org/, and we demonstrate its utility by examining the network response to inhibition of cholesterol synthesis in liver cells and to docetaxel in prostate cancer lines.
能够在任何组织或细胞类型中可靠且可重复地测量人类蛋白质组中的任何蛋白质,对于理解生理和疾病中的系统水平特性以及特定途径将具有变革性意义。在此,我们描述了一组高度特异性检测方法的生成与验证,这些检测方法通过广泛可用、灵敏且稳健的靶向质谱方法——选择反应监测(SRM),能够对20,277种注释的人类蛋白质中的99.7%进行定量。这个人SRM图谱提供了明确的坐标,能够确凿地鉴定生物样品中的相应肽段。我们报告了关于166,174个蛋白质型肽段的数据,这些数据提供了多种独立检测方法来定量任何人类蛋白质以及众多剪接变体、非同义突变和翻译后修饰。这些数据可在http://www.srmatlas.org/ 上作为资源免费获取,并且我们通过研究肝细胞中胆固醇合成抑制以及前列腺癌细胞系中多西他赛的网络反应来证明其效用。