ArticleBMC systems biology2014
Systems biology modeling of omics data: effect of cyclosporine a on the Nrf2 pathway in human renal cells.
Article in BMC systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 66 citations in OpenAlex.
- Oxidative stress in pituitary neuroendocrine tumors: Affecting the tumor microenvironment and becoming a new target for pituitary neuroendocrine tumor therapy.CNS neuroscience & therapeutics · 2023Review
- Predictive power of non-identifiable models.Scientific reports · 2023Article
- Natural Reno-Protective Agents against Cyclosporine A-Induced Nephrotoxicity: An Overview.Molecules (Basel, Switzerland) · 2022Review
- Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway.Redox biology · 2022Review
- Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure.Scientific reports · 2022Article
- Multimeric structure enables the acceleration of KaiB-KaiC complex formation induced by ADP/ATP exchange inhibition.PLoS computational biology · 2022Article
- Inhibition of oxidative stress and apoptosis by camel milk mitigates cyclosporine-induced nephrotoxicity: Targeting Nrf2/HO-1 and AKT/eNOS/NO pathways.Food science & nutrition · 2021Article
- Well-tempered MCMC simulations for population pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making.Toxicological sciences : an official journal of the Society of Toxicology · 2018Review
- Investigation of Nrf2, AhR and ATF4 Activation in Toxicogenomic Databases.Frontiers in genetics · 2018Article
- Computational Models of Reactive Oxygen Species as Metabolic Byproducts and Signal-Transduction Modulators.Frontiers in pharmacology · 2016Review
- From smoking guns to footprints: mining for critical events of toxicity pathways in transcriptome data.Archives of toxicology · 2015Article
- Decoding Cellular Dynamics in Epidermal Growth Factor Signaling Using a New Pathway-Based Integration Approach for Proteomics and Transcriptomics Data.Frontiers in genetics · 2015Article
- Effects of Storage Temperature and Time on Stability of Serum Tacrolimus and Cyclosporine A Levels in Whole Blood by LC-MS/MS.International journal of analytical chemistry · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIncorporation 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.
resultsIn 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 μM CsA repeated exposure. Plateau responses were found at 15 μM 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 μM for CsA in RPTECs.
conclusionsThe 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.