Definitions
The most frequent quantitative definition of noise is the coefficient of variation: : where is the noise in a quantity , is theExperimental measurement
The first experimental account and analysis of gene expression noise in prokaryotes is from Becskei & Serrano and from Alexander van Oudenaarden's lab. The first experimental account and analysis of gene expression noise in eukaryotes is from James J. Collins's lab.Intrinsic and extrinsic noise
Cellular noise is often investigated in the framework of ''intrinsic'' and ''extrinsic'' noise. Intrinsic noise refers to variation in identically-regulated quantities within a single cell: for example, the intra-cell variation in expression levels of two identically-controlled genes. Extrinsic noise refers to variation in identically-regulated quantities between different cells: for example, the cell-to-cell variation in expression of a given gene. Intrinsic and extrinsic noise levels are often compared in dual reporter studies, in which the expression levels of two identically-regulated genes (often fluorescent reporters like GFP and YFP) are plotted for each cell in a population. An issue with the general depiction of extrinsic noise as a spread along the main diagonal in dual-reporter studies is the assumption that extrinsic factors cause positive expression correlations between the two reporters. In fact, when the two reporters compete for binding of a low-copy regulator, the two reporters become anomalously anticorrelated, and the spread is perpendicular to the main diagonal. In fact, any deviation of the dual-reporter scatter plot from circular symmetry indicates extrinsic noise. Information theory offers a way to avoid this anomaly.Sources
''Note'': These lists are illustrative, not exhaustive, and identification of noise sources is an active and expanding area of research. ;Intrinsic noise * ''Low copy-number effects (including discrete birth and death events)'': the random ( stochastic) nature of production and degradation of cellular components means that noise is high for components at low copy number (as the magnitude of these random fluctuations is not negligible with respect to the copy number); * ''Diffusive cellular dynamics'': many important cellular processes rely on collisions between reactants (for example, RNA polymerase and DNA) and other physical criteria which, given the diffusive dynamic nature of the cell, occur stochastically. * ''Noise propagation'': Low copy-number effects and diffusive dynamics result in each of the biochemical reactions in a cell occurring randomly. Stochasticity of reactions can be either attenuated or amplified. Contribution each reaction makes to the intrinsic variability in copy numbers can be quantified via Van Kampen's system size expansion. ;Extrinsic noise * ''Cellular age / cell cycle stage'': cells in a dividing population that is not synchronised will, at a given snapshot in time, be at differentEffects
''Note'': These lists are illustrative, not exhaustive, and identification of noise effects is an active and expanding area of research. * ''Gene expression levels'': noise in gene expression causes differences in the fundamental properties of cells, limits their ability to biochemically control cellular dynamics, and directly or indirectly induce many of the specific effects below; * ''Energy levels and transcription rate'': noise in transcription rate, arising from sources including transcriptional bursting, is a significant source of noise in expression levels of genes. Extrinsic noise in mitochondrial content has been suggested to propagate to differences in the ATP concentrations and transcription rates (with functional relationships implied between these three quantities) in cells, affecting cells' energetic competence and ability to express genes; * ''Phenotype selection'': bacterial populations exploit extrinsic noise to choose a population subset to enter a quiescent state. In a bacterial infection, for example, this subset will not propagate quickly but will be more robust when the population is threatened by antibiotic treatment: the rapidly replicating, infectious bacteria will be killed more quickly than the quiescent subset, which may be capable of restarting the infection. This phenomenon is why courses of antibiotics should be finished even when symptoms seem to have disappeared; * ''Development and stem cell differentiation'': developmental noise in biochemical processes which need to be tightly controlled (for example, patterning of gene expression levels that develop into different body parts) during organismal development can have dramatic consequences, necessitating the evolution of robust cellular machinery.Analysis
As many quantities of cell biological interest are present in discrete copy number within the cell (single DNAs, dozens of mRNAs, hundreds of proteins), tools from discrete stochastic mathematics are often used to analyse and model cellular noise. In particular,References
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