Qualitative modelling and formal verification of the FLR1 gene mancozeb response in Saccharomyces cerevisiae
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- TL;DR
- This study presents a qualitative model and formal verification of the gene regulatory network controlling the response of baker's yeast to the agricultural fungicide mancozeb.
- Problem
- Understanding gene regulatory networks requires analyzing the relationship between their structure and dynamics, but validating models and testing new hypotheses against experimental data is challenging.
- Method
- The authors used qualitative modelling, simulation, and formal verification methods—such as model checking—to analyze the network controlling the FLR1 gene response.
- Results
- The analysis evaluated component regulation levels, confronted model predictions with experimental data, and assessed model robustness to parameter ordering and gene deletion.
- Contributions
- Not specified in the abstract.
- Limitations
- Not specified in the abstract.
- Takeaways
- The work provides a computable model that enables quick, cost-effective hypothesis testing prior to experimental validation, while pointing to the need for a new transcription factor to fully activate YAP1.
- Applications
- Not specified in the abstract.
- Topics
- Systems Biology, Gene Regulatory Networks, Formal Verification
- For industry
- Agriculture
- Why it matters
- Not specified in the abstract.
Abstract
BACKGROUND: Qualitative models allow understanding the relation between the structure and the dynamics of gene regulatory networks. The dynamical properties of these models can be automatically analysed by means of formal verification methods, like model checking. This facilitates the model-validation process and the test of new hypotheses to reconcile model predictions with the experimental data. RESULTS: The authors report in this study the qualitative modelling and simulation of the transcriptional regulatory network controlling the response of the model eukaryote Saccharomyces cerevisiae to the agricultural fungicide mancozeb. The model allowed the analysis of the regulation level and activity of the components of the gene mancozeb-induced network controlling the transcriptional activation of the FLR1 gene, which is proposed to confer multidrug resistance through its putative role as a drug eflux pump. Formal verification analysis of the network allowed us to confront model predictions with the experimental data and to assess the model robustness to parameter ordering and gene deletion. CONCLUSIONS: This analysis enabled us to better understand the mechanisms regulating the FLR1 gene mancozeb response and confirmed the need of a new transcription factor for the full transcriptional activation of YAP1. The result is a computable model of the FLR1 gene response to mancozeb, permitting a quick and cost-effective test of hypotheses prior to experimental validation.