Dynamics of gene expression and the regulatory inference problem

@article{Berg2008DynamicsOG,
  title={Dynamics of gene expression and the regulatory inference problem},
  author={Johannes Berg},
  journal={EPL},
  year={2008},
  volume={82},
  pages={28010}
}
From the response to external stimuli to cell division and death, the dynamics of living cells is based on the expression of specific genes at specific times. The decision when to express a gene is implemented by the binding and unbinding of transcription factor molecules to regulatory DNA. Here, we construct stochastic models of gene expression dynamics and test them on experimental time series data of messenger-RNA concentrations. The models are used to infer biophysical parameters of gene… 

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References

SHOWING 1-10 OF 30 REFERENCES
Reconstructing repressor protein levels from expression of gene targets in Escherichia coli
TLDR
This work considers an example of an SOS repair system, and computationally infer the regulator activity of its master repressor, LexA, and reconstructs a behavior that is similar to the experimentally measured profile of this repressor.
On schemes of combinatorial transcription logic
TLDR
This work shows explicit schemes to implement regulatory logic functions of increasing complexity by appropriately selecting the strengths and arranging the relative positions of the relevant protein-binding DNA sequences in the cis-regulatory region.
Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics
TLDR
The concentration profile of the master SOS transcriptional repressor can be calculated, demonstrating that relative protein levels may be determined from purely transcriptional data, and opening the possibility of assigning kinetic parameters to transcriptional networks on a genomic scale.
Regulation of noise in the expression of a single gene
TLDR
The results provide the first direct experimental evidence of the biochemical origin of phenotypesic noise, demonstrating that the level of phenotypic variation in an isogenic population can be regulated by genetic parameters.
Physical constraints and functional characteristics of transcription factor–DNA interaction
  • U. Gerland, J. Moroz, T. Hwa
  • Biology, Physics
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
The concept of programmability is introduced and motivated, i.e., the ability to set the threshold concentration for TF binding over a wide range merely by mutating the binding sequence of a target site, which indicates that TF–DNA interaction is indeed programmable.
Building a dictionary for genomes: identification of presumptive regulatory sites by statistical analysis.
TLDR
An algorithm, "MobyDick," is presented that decomposes a set of DNA sequences into the most probable dictionary of motifs or words, applicable to any set ofDNA sequences: for example, all upstream regions in a genome or all genes expressed under certain conditions.
Design principles of biological circuits
Stochastic Dynamical Systems: Concepts, Numerical Methods, Data Analysis
TLDR
The book contains various stochastic and mathematical methods which are necessary for the analysis of complex systems such as polymeric melts, the human body and the atmosphere.
Stochastic processes in physics and chemistry
Preface to the first edition. Preface to the second edition. Abbreviated references. I. Stochastic variables. II. Random events. III. Stochastic processes. IV. Markov processes. V. The master
Stochastic Processes in Physics and Chemistry
N G van Kampen 1981 Amsterdam: North-Holland xiv + 419 pp price Dfl 180 This is a book which, at a lower price, could be expected to become an essential part of the library of every physical
...
...