Frequency domain analysis of noise in autoregulated gene circuits. Export

@article{citeulike:202244, abstract = {We describe a frequency domain technique for the analysis of intrinsic noise within negatively autoregulated gene circuits. This approach is based on the transfer function around the feedback loop (loop transmission) and the equivalent noise bandwidth of the system. The loop transmission, T, is shown to be a determining factor of the dynamics and the noise behavior of autoregulated gene circuits, and this T-based technique provides a simple and flexible method for the analysis of noise arising from any source within the gene circuit. We show that negative feedback not only reduces the variance of the noise in the protein concentration, but also shifts this noise to higher frequencies where it may have a negligible effect on the noise behavior of following gene circuits within a cascade. This predicted effect is demonstrated through the exact stochastic simulation of a two-gene cascade. The analysis elucidates important aspects of gene circuit structure that control functionality, and may provide some insights into selective pressures leading to this structure. The resulting analytical relationships have a simple form, making them especially useful as synthetic gene circuit design equations. With the exception of the linearization of Hill kinetics, this technique is general and may be applied to the analysis or design of networks of higher complexity. This utility is demonstrated through the exact stochastic simulation of an autoregulated two-gene cascade operating near instability.}, address = {Molecular Scale Engineering and Nanoscale Technologies Research Group, Oak Ridge National Laboratory, P.O. Box 2008, MS 6006, Oak Ridge, TN 37831-6006, USA. simpsonML1@ornl.gov}, author = {Simpson, Michael L. and Cox, Chris D. and Sayler, Gary S.}, citeulike-article-id = {202244}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0736140100}, citeulike-linkout-1 = {http://www.pnas.org/content/100/8/4551.full.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/100/8/4551.full.full.pdf}, citeulike-linkout-3 = {http://www.pnas.org/cgi/content/abstract/100/8/4551}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/12671069}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=12671069}, day = {15}, doi = {10.1073/pnas.0736140100}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {circuit, feedback, gene, noise, stochastic, synthetic}, month = {April}, number = {8}, pages = {4551--4556}, posted-at = {2007-08-16 20:18:51}, priority = {0}, title = {Frequency domain analysis of noise in autoregulated gene circuits.}, url = {http://dx.doi.org/10.1073/pnas.0736140100}, volume = {100}, year = {2003} }

TY - JOUR ID - citeulike:202244 L3 - citeulike-article-id:202244 N2 - We describe a frequency domain technique for the analysis of intrinsic noise within negatively autoregulated gene circuits. This approach is based on the transfer function around the feedback loop (loop transmission) and the equivalent noise bandwidth of the system. The loop transmission, T, is shown to be a determining factor of the dynamics and the noise behavior of autoregulated gene circuits, and this T-based technique provides a simple and flexible method for the analysis of noise arising from any source within the gene circuit. We show that negative feedback not only reduces the variance of the noise in the protein concentration, but also shifts this noise to higher frequencies where it may have a negligible effect on the noise behavior of following gene circuits within a cascade. This predicted effect is demonstrated through the exact stochastic simulation of a two-gene cascade. The analysis elucidates important aspects of gene circuit structure that control functionality, and may provide some insights into selective pressures leading to this structure. The resulting analytical relationships have a simple form, making them especially useful as synthetic gene circuit design equations. With the exception of the linearization of Hill kinetics, this technique is general and may be applied to the analysis or design of networks of higher complexity. This utility is demonstrated through the exact stochastic simulation of an autoregulated two-gene cascade operating near instability. IS - 8 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - Molecular Scale Engineering and Nanoscale Technologies Research Group, Oak Ridge National Laboratory, P.O. Box 2008, MS 6006, Oak Ridge, TN 37831-6006, USA. simpsonML1@ornl.gov EP - 4556 TI - Frequency domain analysis of noise in autoregulated gene circuits. VL - 100 SP - 4551 KW - circuit KW - feedback KW - gene KW - noise KW - stochastic KW - synthetic AU - Simpson, Michael AU - Cox, Chris AU - Sayler, Gary PY - 2003/04/15/ UR - http://dx.doi.org/10.1073/pnas.0736140100 ER -