A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis

被引:214
作者
Picotti, Paola [1 ,2 ]
Clement-Ziza, Mathieu [3 ]
Lam, Henry [4 ,5 ]
Campbell, David S. [6 ]
Schmidt, Alexander [7 ]
Deutsch, Eric W. [6 ]
Roest, Hannes [1 ]
Sun, Zhi [6 ]
Rinner, Oliver [1 ,8 ]
Reiter, Lukas [1 ,8 ]
Shen, Qin [1 ,9 ]
Michaelson, Jacob J. [3 ]
Frei, Andreas [1 ]
Alberti, Simon [10 ]
Kusebauch, Ulrike [6 ]
Wollscheid, Bernd [1 ]
Moritz, Robert L. [6 ]
Beyer, Andreas [3 ]
Aebersold, Ruedi [1 ,11 ,12 ]
机构
[1] ETH, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland
[2] ETH, Inst Biochem, Dept Biol, CH-8093 Zurich, Switzerland
[3] Tech Univ Dresden, Ctr Biotechnol, D-01069 Dresden, Germany
[4] Hong Kong Univ Sci & Technol, Dept Chem & Biomol Engn, Hong Kong, Hong Kong, Peoples R China
[5] Hong Kong Univ Sci & Technol, Div Biomed Engn, Hong Kong, Hong Kong, Peoples R China
[6] Inst Syst Biol, Seattle, WA 98103 USA
[7] Univ Basel, Prote Core Facil Biozentrum, CH-4056 Basel, Switzerland
[8] Biognosys AG, CH-8093 Zurich, Switzerland
[9] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China
[10] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany
[11] Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland
[12] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland
基金
美国国家科学基金会; 瑞士国家科学基金会; 欧洲研究理事会; 美国国家卫生研究院;
关键词
SACCHAROMYCES-CEREVISIAE; PEPTIDE IDENTIFICATION; BUDDING YEAST; EXPRESSION; PREDICTION; LIBRARIES; PROTEINS; SEQUENCE; TANDEM; ASSAYS;
D O I
10.1038/nature11835
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Experience from different fields of life sciences suggests that accessible, complete reference maps of the components of the system under study are highly beneficial research tools. Examples of such maps include libraries of the spectroscopic properties of molecules, or databases of drug structures in analytical or forensic chemistry. Such maps, and methods to navigate them, constitute reliable assays to probe any sample for the presence and amount of molecules contained in the map. So far, attempts to generate such maps for any proteome have failed to reach complete proteome coverage(1-3). Here we use a strategy based on high-throughput peptide synthesis and mass spectrometry to generate an almost complete reference map (97% of the genome-predicted proteins) of the Saccharomyces cerevisiae proteome. We generated two versions of this mass-spectrometric map, one supporting discovery-driven (shotgun)(3,4) and the other supporting hypothesis-driven (targeted)(5,6) proteomic measurements. Together, the two versions of the map constitute a complete set of proteomic assays to support most studies performed with contemporary proteomic technologies. To show the utility of the maps, we applied them to a protein quantitative trait locus (QTL) analysis(7), which requires precise measurement of the same set of peptides over a large number of samples. Protein measurements over 78 S. cerevisiae strains revealed a complex relationship between independent genetic loci, influencing the levels of related proteins. Our results suggest that selective pressure favours the acquisition of sets of polymorphisms that adapt protein levels but also maintain the stoichiometry of functionally related pathway members.
引用
收藏
页码:266 / 270
页数:5
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