Single-cell proteomic analysis of S-cerevisiae reveals the architecture of biological noise

被引:1158
作者
Newman, John R. S.
Ghaemmaghami, Sina
Ihmels, Jan
Breslow, David K.
Noble, Matthew
DeRisi, Joseph L.
Weissman, Jonathan S.
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94107 USA
[2] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94107 USA
[3] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94107 USA
[4] Calif Inst Quantitat Biomed Res, San Francisco, CA 94107 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature04785
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
A major goal of biology is to provide a quantitative description of cellular behaviour. This task, however, has been hampered by the difficulty in measuring protein abundances and their variation. Here we present a strategy that pairs high-throughput flow cytometry and a library of GFP-tagged yeast strains to monitor rapidly and precisely protein levels at single-cell resolution. Bulk protein abundance measurements of >2,500 proteins in rich and minimal media provide a detailed view of the cellular response to these conditions, and capture many changes not observed by DNA microarray analyses. Our single-cell data argue that noise in protein expression is dominated by the stochastic production/destruction of messenger RNAs. Beyond this global trend, there are dramatic protein-specific differences in noise that are strongly correlated with a protein's mode of transcription and its function. For example, proteins that respond to environmental changes are noisy whereas those involved in protein synthesis are quiet. Thus, these studies reveal a remarkable structure to biological noise and suggest that protein noise levels have been selected to reflect the costs and potential benefits of this variation.
引用
收藏
页码:840 / 846
页数:7
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