We also sought to develop methods to analyse splicing varia

The resulting network, shown in Additional File 2 contains 223 molecules linked to CRKL. In order to use the pathway diagram as a resource for modelling the CRKL network, and to simulate a dynamic element, the Signalling Petri Net supplier JNJ-7706621 algorithm pro posed in was adopted. Petri Net Petri net models, first described in 1939, character ise the dynamics of signal flow using token distribution and sampling. Specifically, a Petri net is a directed net work in which nodes are connected by transitions, where the edges describe the conditions for which transitions can occur. Nodes in a Petri net contain a discrete num ber of tokens, the distribution of which across all nodes describes the state of the system. In a Petri net a transi tion causes the number of tokens at a node to change by firing whenever there are sufficient tokens at the start ing node of an edge.<br><br> When a transition 価格 LDN193189 fires, tokens are placed at the end node of the edge over which the tran sition occurs. The execution of a Petri net is nondeter ministic so that when multiple transitions are enabled at the same time any one of them may fire, thus representing the stochastic nature of the system. Signalling Petri net extends the Petri net model by allowing for nonparametric modelling of cellular sig nalling networks; adding a simulator for modelling the average flow of tokens over multiple time steps, Compared to Petri nets, SPN can model different transi tions and different node types, corresponding to those available in the commonly used System Biology Mark up Language, SBML is a machine readable format for representing models, oriented towards describing systems where biological entities are involved in, and modified by, processes that occur over time, SBML is particularly suitable for representing models com monly found in research on cell signalling pathways, metabolic pathways, biochemical reactions and gene regulation to give examples, thus making it an ap propriate language to adopt here.<br><br> A major advantage of using software based on SBML is that it allows the sys tems biology buy LY2228820 community to share, evaluate and coopera tively develop models. The addition of a simulator in SPN allows for one to repeat the process of firing tokens over multiple time blocks and to determine the state of a system on average and after perturbation.<br><br> Here, using BioLayout Express, a software for the visualisation of biological data as net works that incorporates SPN, it was possible to allow each node of the CRKL sub network to represent a molecule and the number of tokens associated with a node at each time point to represent its expression level. Network simulation By altering the number of tokens associated with CRKL at time t 0, BioLayout Express was used to simulate a change in expression level of CRKL and the potential consequential effect on the CRKL sub network. To achieve this, the CRKL sub network was first trans formed by adding transition gates to the network. Nodes at the edge of the network representing the beginning of a path were assigned 100 tokens at time zero.