We introduce the Dynamic Influence Network (DIN), a novel visual analytics technique for representing and analyzing rule-based models of protein-protein interaction networks. Rule-based modeling has proved instrumental in developing biological models that are concise, comprehensible, easily extensible, and that mitigate the combinatorial complexity of multi-state and multi-component biological molecules. Our technique visualizes the dynamics of these rules as they evolve over time. Using the data produced by KaSim, an open source stochastic simulator of rule-based models written in the Kappa language, DINs provide a node-link diagram that represents the influence that each rule has on the other rules. That is, rather than representing individual biological components or types, we instead represent the rules about them (as nodes) and the current influence of these rules (as links). Using our interactive DIN-Viz software tool, researchers are able to query this dynamic network to find meaningful patterns about biological processes, and to identify salient aspects of complex rule-based models. To evaluate the effectiveness of our approach, we investigate a simulation of a circadian clock model that illustrates the oscillatory behavior of the KaiC protein phosphorylation cycle.
@cite_29 provide an overview of graphical modeling software tools for representing or simulating reaction-based models, and detailing usability and perceptual issues that they can introduce. They find that creating graphical languages with many glyphs reduces ambiguity, but at the cost of introducing visual clutter and making the visual layout unappealing to users. They advocate for a minimalist approach that presents only the visual elements necessary for a particular analysis. Our tool also uses a smaller visual language for representing rules and clusters of rules.
@cite_29
2011257065
Modeling biological systems to understand their mechanistic behavior is an important activity in molecular systems biology. Mathematical modeling typically requires deep mathematical or computing knowledge, and this limits the spread of modeling tools among biologists. Graphical modeling languages have been introduced to minimize this limit. Here, we survey the main graphical formalisms (supported by software tools) available to model biological systems with a primary focus on their usability, within the framework of modeling reaction pathways with two-dimensional (2D) (possibly nested) compartments. Considering the main characteristics of the surveyed formalisms, we synthesise a new proposal (Style) and report the results of an online survey conducted among biologists to assess usability of available graphical formalisms. We consider this proposal a guideline developed from what we learned in the survey, which can inform development of graphical formalisms to model reaction pathways in 2D space.