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

JRS Newman, S Ghaemmaghami, J Ihmels… - Nature, 2006 - nature.com
JRS Newman, S Ghaemmaghami, J Ihmels, DK Breslow, M Noble, JL DeRisi, JS Weissman
Nature, 2006nature.com
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 …
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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