Methodologies for the modeling and simulation of biochemical networks, illustrated for signal transduction pathways: A primer

Biochemical networks depict the chemical interactions that take place among elements of living cells. They aim to elucidate how cellular behavior and functional properties of the cell emerge from the relationships between its components, i.e. molecules. Biochemical networks are largely characterized by dynamic behavior, and exhibit high degrees of complexity. Hence, the interest in such networks is growing and they have been the target of several recent modeling efforts. Signal transduction pathways (STPs) constitute a class of biochemical networks that receive, process, and respond to stimuli from the environment, as well as stimuli that are internal to the organism. An STP consists of a chain of intracellular signaling processes that ultimately result in generating different cellular responses. This primer presents the methodologies used for the modeling and simulation of biochemical networks, illustrated for STPs. These methodologies range from qualitative to quantitative, and include structural as well as dynamic analysis techniques. We describe the different methodologies, outline their underlying assumptions, and provide an assessment of their advantages and disadvantages. Moreover, publicly and/or commercially available implementations of these methodologies are listed as appropriate. In particular, this primer aims to provide a clear introduction and comprehensive coverage of biochemical modeling and simulation methodologies for the non-expert, with specific focus on relevant literature of STPs.