Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.
Bottom Line: The gene regulatory network (GRN) is the central decision-making module of the cell.BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response.BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation.
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom firstname.lastname@example.org.Show MeSH
Related in: MedlinePlus
Mentions: Although BQS has been developed here in the context of GRNs, it provides general principles that can be used to analyse or manipulate robustness in any regulatory system, biological or otherwise. These principles are summarised by five simple rules (Figure 10): 1. Avoid long feedback loops to minimize instability arising from perturbations in network interactions (the basic principle of Qualitative Stability); 2. Favour constitutive (unregulated) nodes to reduce the potential number of loops; 3. Avoid long paths to minimize the number of ‘incomplete feedback loops’ and the emergence of instability due to addition of new network connections; 4. Favour buffered motifs over unbuffered motifs to reduce the potential number of loops; 5. Avoid centralized control hubs with a large number of both regulatory and regulating connections to reduce potential instability (necessitating the use of distributed control). These rules can be used to devise highly stable networks that minimize the ‘hyper-risk’ inherent in global networks that are difficult to control (Helbing, 2013).10.7554/eLife.02863.037Figure 10.BQS Rules.
Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom email@example.com.