Developing time constraints in Petri net models of biochemical processes via computation structure modeling

Abstract

Computation structure modeling can be applied to a model of a biochemical process. We present an application of computation structure model analysis to a published Petri net model of part of an inflammation process. From this computation structure model and published experimental data we develop a timing constraint. Because the number of possible biochemical reactions in the human cell is distressingly large, recognizing existing constraints upon what reactions can occur, such as when potential reactants are sequestered in different compartments, or steric constraints prohibit docking, provides needed reduction of these possibilities. Modeling with networks, including Petri nets, is common in systems biology and constraint application can be visualized acting upon these graphs, pruning subtrees from a network of possibilities. The technique is complementary to stochastic simulations algorithms and to T and P-invariant analysis of Petri nets. We apply the modeling technique to spliceosome acting on C9ORF72 intronic hexanucleotide repeats, to illustrate one effect of this repeat on splicing.