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

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          Abstract

          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.

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          Author and article information

          Journal
          Nature
          Nature
          Springer Science and Business Media LLC
          1476-4687
          0028-0836
          Jun 15 2006
          : 441
          : 7095
          Affiliations
          [1 ] Howard Hughes Medical Institute, San Francisco, California, USA. jrsnewman@alum.mit.edu
          Article
          nature04785
          10.1038/nature04785
          16699522
          7d31f554-749a-428a-b052-7b481758ba1d
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