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

John R.S. Newman, Sina Ghaemmaghami, Jan Ihmels, David K. Breslow, Matthew Noble, Joseph L. DeRisi, Jonathan S. Weissman

Research output: Contribution to journalArticlepeer-review

1078 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)840-846
Number of pages7
JournalNature
Volume441
Issue number7095
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • General

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