Dataset Information

Systems biology modeling of omics data: effect of cyclosporine a on the Nrf2 pathway in human renal cells.

ABSTRACT:

Background

Incorporation of omic data streams for building improved systems biology models has great potential for improving their predictions of biological outcomes. We have recently shown that cyclosporine A (CsA) strongly activates the nuclear factor (erythroid-derived 2)-like 2 pathway (Nrf2) in renal proximal tubular epithelial cells (RPTECs) exposed in vitro. We present here a quantitative calibration of a differential equation model of the Nrf2 pathway with a subset of the omics data we collected.

Results

In vitro pharmacokinetic data on CsA exchange between cells, culture medium and vial walls, and data on the time course of omics markers in response to CsA exposure were reasonably well fitted with a coupled PK-systems biology model. Posterior statistical distributions of the model parameter values were obtained by Markov chain Monte Carlo sampling in a Bayesian framework. A complex cyclic pattern of ROS production and control emerged at 5 ?M CsA repeated exposure. Plateau responses were found at 15 ?M exposures. Shortly above those exposure levels, the model predicts a disproportionate increase in cellular ROS quantity which is consistent with an in vitro EC50 of about 40 ?M for CsA in RPTECs.

Conclusions

The model proposed can be used to analyze and predict cellular response to oxidative stress, provided sufficient data to set its parameters to cell-specific values. Omics data can be used to that effect in a Bayesian statistical framework which retains prior information about the likely parameter values.

SUBMITTER: Hamon J

PROVIDER: S-EPMC4089556 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Systems biology modeling of omics data: effect of cyclosporine a on the Nrf2 pathway in human renal cells.

Hamon Jérémy J Jennings Paul P Bois Frederic Y FY

BMC systems biology 20140625

<h4>Background</h4>Incorporation of omic data streams for building improved systems biology models has great potential for improving their predictions of biological outcomes. We have recently shown that cyclosporine A (CsA) strongly activates the nuclear factor (erythroid-derived 2)-like 2 pathway (Nrf2) in renal proximal tubular epithelial cells (RPTECs) exposed in vitro. We present here a quantitative calibration of a differential equation model of the Nrf2 pathway with a subset of the omics d ...[more]

PMID: 24964791

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Dataset Information

Systems biology modeling of omics data: effect of cyclosporine a on the Nrf2 pathway in human renal cells.

Background

Results

Conclusions

Publications

Systems biology modeling of omics data: effect of cyclosporine a on the Nrf2 pathway in human renal cells.

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