Fig 1.
(A) The 1965 and the present-day Central Dogma editions in molecular biology (B) The initial four-node Central Dogma wiring diagram formed by DNA, mRNA, Protein and Activator. (C) The present-day seven-node Central Dogma wiring diagram formed by DNA, mRNA, Protein, Activator, miRNA, DegProtein and DegRNA. The directed edge “—o” represents a functional relationship with both activatory and inhibitory effects (D) Network representation of Boolean rules corresponding to the simple 1965 model. (E) Network representation of Boolean rules corresponding to the present-day updated model. For simplicity, the first version of each model is shown.
Table 1.
Boolean rules governing the state of the 4-node network of the 1965 proposed central dogma depicted in Fig 1B derived from [1, 2].
The symbols “&”, “|” and “!” represent “AND”, “OR” and “NOT” operators.
Table 2.
Boolean rules governing the state of the 7-node network of the present-day central dogma depicted in Fig 1C derived from [1–3, 7–11, 20, 21].
The symbols “&”, “|” and “!” represent “AND”, “OR” and “NOT” operators.
Table 3.
The probabilistic version of the combined Boolean network of the present-day central dogma.
The symbols “&”, “|” and “!” represent “AND”, “OR” and “NOT” operators.
Table 4.
The attractors of the Boolean model as depicted in Fig 1B obtained from the synchronous update method.
In each version of the model, the number of single SSs and the corresponding normalized basin of attractions are demonstrated. The color gradient from red, yellow to green illustrate the lowest to the highest values, respectively. A to K attractors are encoded in the following order: Activator/DNA/mRNA/Protein. The D*, H* and K* denote specific states pertaining to this Central Dogma modeling.
Table 5.
The attractors of the Boolean model depicted in Fig 1C obtained from the synchronous update method.
In each version of the model, demonstrated are the number of single SSs, SSs with multiple states (limit cycles) and corresponding normalized basin of attractions. The color gradient from red, yellow to green illustrate the lowest to highest values. The attractors A to I are encoded in the following order: Activator/DegProtein/DegRNA/DNA/miRNA/mRNA/Protein.
Fig 2.
Network visualization of the complex (loose) attractor in the present-day model.
Node size and color are proportional to betweenness and closeness centrality measures respectively.
Table 6.
The attractors of the Boolean model depicted in Fig 1C obtained from the asynchronous updating method.
Each version of the model illustrated the presence of simple attractors, the complex (loose) attractor and corresponding edge numbers in the latter. The binary digits (0 and 1) of the attractors (A to H) from left to right indicate the state of the components Activator, DegProtein, DegRNA, DNA, miRNA, mRNA and protein.
Table 7.
The absorption probabilities for the Markov chain corresponding to the Boolean model depicted in Fig 1C in all versions.
These probabilities were estimated based on 1000 iterations. The last column represents the absorption probabilities of the probabilistic Boolean network of the present-day Central Dogma (See Table 2).
Table 8.
The robustness analysis of the reconstructed models of the central dogma.