Systems Biology (Methods in Molecular Biology)

model is constructed in CellNetAnalyzer, a MATLAB tool to carry

out structural and dynamical analysis (here we used a logical steady

state) of a large system of interactions. In the logical steady state,

the signal drives from input to output of system for all species and

reactions until no further state update. All the Boolean functions

are derived from the network structure (seeTable2). The ligand

EGF, DNA damage, PTEN, and DP1 are input node while TP53

and E2F1 regulated apoptotic genes [68] are the output of the

systems. In Table2 reactions, which are derived from the pathway

shown in Fig.9, Boolean functions are shown in the CellNetAna-

lyzer format. Species on the left-hand side of the equation represent

“Reactants” and the species and the right-hand side represents

“Products.” The “Coefficient” indicates the level of expression of

reactants and products. The “þ“ sign represent “AND” logic and

the “!“ sign is used for “NOT.”

Fig. 9Logic-based model of signaling and transcriptional pathway in cancer: The

blackandred linesrepresent the type of interactions (i.e., activation and

inhibition respectively) among the interacting components. Nodes attached by

green boxandarroware the input, while the nodes attached withyellow boxand

arroware the output nodes of the system. The model is constructed in ProMoT

[69] and layout of the graphic is produced in yEd

260 Faiz M. Khan et al.