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Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments

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Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments. / Rapsomaniki, M.A.; Cinquemani, E.; Giakoumakis, N.N. et al.
In: Bioinformatics, Vol. 31, No. 3, 28.02.2015, p. 355-362.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Rapsomaniki, MA, Cinquemani, E, Giakoumakis, NN, Kotsantis, P, Lygeros, J & Lygerou, Z 2015, 'Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments', Bioinformatics, vol. 31, no. 3, pp. 355-362. https://doi.org/10.1093/bioinformatics/btu619

APA

Rapsomaniki, M. A., Cinquemani, E., Giakoumakis, N. N., Kotsantis, P., Lygeros, J., & Lygerou, Z. (2015). Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments. Bioinformatics, 31(3), 355-362. https://doi.org/10.1093/bioinformatics/btu619

Vancouver

Rapsomaniki MA, Cinquemani E, Giakoumakis NN, Kotsantis P, Lygeros J, Lygerou Z. Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments. Bioinformatics. 2015 Feb 28;31(3):355-362. doi: 10.1093/bioinformatics/btu619

Author

Rapsomaniki, M.A. ; Cinquemani, E. ; Giakoumakis, N.N. et al. / Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments. In: Bioinformatics. 2015 ; Vol. 31, No. 3. pp. 355-362.

Bibtex

@article{bc85217df1f24826b441cb247b764b73,
title = "Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments",
abstract = "Motivation : Fluorescence recovery after photobleaching (FRAP) is a functional live cell imaging technique that permits the exploration of protein dynamics in living cells. To extract kinetic parameters from FRAP data, a number of analytical models have been developed. Simplifications are inherent in these models, which may lead to inexhaustive or inaccurate exploitation of the experimental data. An appealing alternative is offered by the simulation of biological processes in realistic environments at a particle level. However, inference of kinetic parameters using simulation-based models is still limited.Results : We introduce and demonstrate a new method for the inference of kinetic parameter values from FRAP data. A small number of in silico FRAP experiments is used to construct a mapping from FRAP recovery curves to the parameters of the underlying protein kinetics. Parameter estimates from experimental data can then be computed by applying the mapping to the observed recovery curves. A bootstrap process is used to investigate identifiability of the physical parameters and determine confidence regions for their estimates. Our method circumvents the computational burden of seeking the best-fitting parameters via iterative simulation. After validation on synthetic data, the method is applied to the analysis of the nuclear proteins Cdt1, PCNA and GFPnls. Parameter estimation results from several experimental samples are in accordance with previous findings, but also allow us to discuss identifiability issues as well as cell-to-cell variability of the protein kinetics.Implementation : All methods were implemented in MATLAB R2011b. Monte Carlo simulations were run on the HPC cluster Brutus of ETH Zurich.",
author = "M.A. Rapsomaniki and E. Cinquemani and N.N. Giakoumakis and P. Kotsantis and J. Lygeros and Z. Lygerou",
year = "2015",
month = feb,
day = "28",
doi = "10.1093/bioinformatics/btu619",
language = "English",
volume = "31",
pages = "355--362",
journal = "Bioinformatics",
issn = "1367-4803",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments

AU - Rapsomaniki, M.A.

AU - Cinquemani, E.

AU - Giakoumakis, N.N.

AU - Kotsantis, P.

AU - Lygeros, J.

AU - Lygerou, Z.

PY - 2015/2/28

Y1 - 2015/2/28

N2 - Motivation : Fluorescence recovery after photobleaching (FRAP) is a functional live cell imaging technique that permits the exploration of protein dynamics in living cells. To extract kinetic parameters from FRAP data, a number of analytical models have been developed. Simplifications are inherent in these models, which may lead to inexhaustive or inaccurate exploitation of the experimental data. An appealing alternative is offered by the simulation of biological processes in realistic environments at a particle level. However, inference of kinetic parameters using simulation-based models is still limited.Results : We introduce and demonstrate a new method for the inference of kinetic parameter values from FRAP data. A small number of in silico FRAP experiments is used to construct a mapping from FRAP recovery curves to the parameters of the underlying protein kinetics. Parameter estimates from experimental data can then be computed by applying the mapping to the observed recovery curves. A bootstrap process is used to investigate identifiability of the physical parameters and determine confidence regions for their estimates. Our method circumvents the computational burden of seeking the best-fitting parameters via iterative simulation. After validation on synthetic data, the method is applied to the analysis of the nuclear proteins Cdt1, PCNA and GFPnls. Parameter estimation results from several experimental samples are in accordance with previous findings, but also allow us to discuss identifiability issues as well as cell-to-cell variability of the protein kinetics.Implementation : All methods were implemented in MATLAB R2011b. Monte Carlo simulations were run on the HPC cluster Brutus of ETH Zurich.

AB - Motivation : Fluorescence recovery after photobleaching (FRAP) is a functional live cell imaging technique that permits the exploration of protein dynamics in living cells. To extract kinetic parameters from FRAP data, a number of analytical models have been developed. Simplifications are inherent in these models, which may lead to inexhaustive or inaccurate exploitation of the experimental data. An appealing alternative is offered by the simulation of biological processes in realistic environments at a particle level. However, inference of kinetic parameters using simulation-based models is still limited.Results : We introduce and demonstrate a new method for the inference of kinetic parameter values from FRAP data. A small number of in silico FRAP experiments is used to construct a mapping from FRAP recovery curves to the parameters of the underlying protein kinetics. Parameter estimates from experimental data can then be computed by applying the mapping to the observed recovery curves. A bootstrap process is used to investigate identifiability of the physical parameters and determine confidence regions for their estimates. Our method circumvents the computational burden of seeking the best-fitting parameters via iterative simulation. After validation on synthetic data, the method is applied to the analysis of the nuclear proteins Cdt1, PCNA and GFPnls. Parameter estimation results from several experimental samples are in accordance with previous findings, but also allow us to discuss identifiability issues as well as cell-to-cell variability of the protein kinetics.Implementation : All methods were implemented in MATLAB R2011b. Monte Carlo simulations were run on the HPC cluster Brutus of ETH Zurich.

U2 - 10.1093/bioinformatics/btu619

DO - 10.1093/bioinformatics/btu619

M3 - Journal article

VL - 31

SP - 355

EP - 362

JO - Bioinformatics

JF - Bioinformatics

SN - 1367-4803

IS - 3

ER -