Abstract
In this paper, we introduce a unified approach for querying simulation traces of rule-based models about the statistical behavior of individual agents. In our approach, a query consists in a trace pattern along with an expression that depends on the variables captured by this pattern. On a given trace, it evaluates to the multiset of all values of the expression for every possible matching of the pattern. We illustrate our proposed query language on a simple example, and then discuss its semantics and implementation for the Kappa language. Finally, we provide a detailed use case where we analyze the dynamics of \(\beta \)-catenin degradation in Wnt signaling from an agent-centric perspective.
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- 1.
Note that multisets are indicated in Fig. 2 using Dijkstra’s bag notation, whereas sets are indicated using the standard curly brackets notation.
- 2.
Note that functions always take a single argument, which can be a tuple.
- 3.
As defined in Sect. 3.1.
- 4.
Every line of an output file represents a single value. In our expression language, values are tuples of base values. These are separated by commas within a line.
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This work was sponsored by the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army Research Office under grant numbers W911NF-14-1-0367 and W911NF-17-1-0073.
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A Use Case Appendix
A Use Case Appendix
Concentration Time Traces. From the output of the simulator, we get the evolution of the abundance of Cat through time. In Fig. 7, we can see that the systems with low phosphatase behave similarly, even though one has five times the amount of kinases than the other (blue vs red traces). In contrast, the system with high phosphatase shows markedly less degradation of Cat; where the other two systems degraded around 450 units, this one has only degraded 23. From this whole-system view, it would seem the amount of phosphatase is more critical than the amount of kinase: based on the 1:1 system, increasing the kinase five-fold has little effect, whereas increasing the phosphatase has a more dramatic effect.
Tracking the abundance of agent cat through the simulation. At time \(T=0\), the agents are introduced, all in monomeric form. The simulation was stopped after five hundred simulated seconds. In this legend and throughout the figures, “ph” stands for phosphatase, “ki” stands for kinase, and numbers indicate agent multiplicity. Thus “10 ph: 50 ki” means the system with 10 units of phosphatase and 50 of kinase. (Color figure online)
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Laurent, J., Medina-Abarca, H.F., Boutillier, P., Yang, J., Fontana, W. (2018). A Trace Query Language for Rule-Based Models. In: Češka, M., Šafránek, D. (eds) Computational Methods in Systems Biology. CMSB 2018. Lecture Notes in Computer Science(), vol 11095. Springer, Cham. https://doi.org/10.1007/978-3-319-99429-1_13
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