Attractors are less stable than their basins: Canalization creates a coherence gap in gene regulatory networks
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View abstract on PubMed
Summary
This summary is machine-generated.Cellular differentiation is robust due to canalization, which stabilizes development but makes mature cell states less stable, allowing for plasticity. This revises Waddington's epigenetic landscape model.
Area Of Science
- Systems Biology
- Developmental Biology
- Computational Biology
Background
- Waddington's epigenetic landscape metaphor models cellular differentiation.
- Boolean networks formalize gene regulatory dynamics and landscapes.
- Traditional stability measures inadequately assess attractor robustness.
Purpose Of The Study
- Formalize and analyze attractor coherence for stability of cell phenotypes.
- Investigate the stability paradox between attractors and developmental trajectories.
- Understand the role of canalization in biological robustness and plasticity.
Main Methods
- Analyzed 122 expert-curated biological Boolean models.
- Performed large-scale simulations of random gene regulatory networks.
- Quantified attractor coherence and network bias.
Main Results
- Mature cell attractors are less stable than developmental trajectories.
- A coherence gap exists, with attractors near basin boundaries.
- Canalization, while ensuring developmental robustness, creates this gap.
- Network bias strongly predicts the coherence gap magnitude (<math><mi>ρ</mi> <mo>=</mo> <mo>-</mo> <mn>0.997</mn></math>).
Conclusions
- Canalization creates robust development and allows for phenotypic plasticity.
- Findings revise Waddington's landscape, explaining dual robustness and plasticity.
- Implications for understanding development, disease, and synthetic biology circuits.
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