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_46 survey biological pathway visualization projects and introduce a taxonomy of visualization tasks for the analysis of biological pathway data. Relevant tasks are organized in a high-level categorization as tasks, tasks, and tasks. Interestingly, simulations of rule-based models are not explicitly discussed. However, this taxonomy does describe tasks that are relevant to visualizations of rule-based models, and our approach in particular, such as @cite_17 @cite_15 @cite_28 , @cite_54 @cite_53 @cite_5 @cite_41 @cite_40 , and @cite_7 @cite_42 @cite_14 .
@cite_14 @cite_7 @cite_15 @cite_28 @cite_41 @cite_54 @cite_53 @cite_42 @cite_40 @cite_5 @cite_46 @cite_17
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Biological pathway maps are highly relevant tools for many tasks in molecular biology. They reduce the complexity of the overall biological network by partitioning it into smaller manageable parts. While this reduction of complexity is their biggest strength, it is, at the same time, their biggest weakness. By removing what is deemed not important for the primary function of the pathway, biologists lose the ability to follow and understand cross-talks between pathways. Considering these cross-talks is, however, critical in many analysis scenarios, such as judging effects of drugs. In this paper we introduce Entourage, a novel visualization technique that provides contextual information lost due to the artificial partitioning of the biological network, but at the same time limits the presented information to what is relevant to the analyst's task. We use one pathway map as the focus of an analysis and allow a larger set of contextual pathways. For these context pathways we only show the contextual subsets, i.e., the parts of the graph that are relevant to a selection. Entourage suggests related pathways based on similarities and highlights parts of a pathway that are interesting in terms of mapped experimental data. We visualize interdependencies between pathways using stubs of visual links, which we found effective yet not obtrusive. By combining this approach with visualization of experimental data, we can provide domain experts with a highly valuable tool. We demonstrate the utility of Entourage with case studies conducted with a biochemist who researches the effects of drugs on pathways. We show that the technique is well suited to investigate interdependencies between pathways and to analyze, understand, and predict the effect that drugs have on different cell types. Jointly analyzing biological pathway maps and experimental data is critical for understanding how biological processes work in different conditions and why different samples exhibit certain characteristics. This joint analysis, however, poses a significant challenge for visualization. Current techniques are either well suited to visualize large amounts of pathway node attributes, or to represent the topology of the pathway well, but do not accomplish both at the same time. To address this we introduce enRoute, a technique that enables analysts to specify a path of interest in a pathway, extract this path into a separate, linked view, and show detailed experimental data associated with the nodes of this extracted path right next to it. This juxtaposition of the extracted path and the experimental data allows analysts to simultaneously investigate large amounts of potentially heterogeneous data, thereby solving the problem of joint analysis of topology and node attributes. As this approach does not modify the layout of pathway maps, it is compatible with arbitrary graph layouts, including those of hand-crafted, image-based pathway maps. We demonstrate the technique in context of pathways from the KEGG and the Wikipathways databases. We apply experimental data from two public databases, the Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) that both contain a wide variety of genomic datasets for a large number of samples. In addition, we make use of a smaller dataset of hepatocellular carcinoma and common xenograft models. To verify the utility of enRoute, domain experts conducted two case studies where they explore data from the CCLE and the hepatocellular carcinoma datasets in the context of relevant pathways. Background Biologists make use of pathway visualization tools for a range of tasks, including investigating inter-pathway connectivity and retrieving details about biological entities and interactions. Some of these tasks require an understanding of the hierarchical nature of elements within the pathway or the ability to make comparisons between multiple pathways. We introduce a technique inspired by LineSets that enables biologists to fulfill these tasks more effectively. Do visual tasks have a relationship, or are they unrelated? For instance, could having surface normals simplify estimating the depth of an image? Intuition answers these questions positively, implying existence of a structure among visual tasks. Knowing this structure has notable values; it is the concept underlying transfer learning and provides a principled way for identifying redundancies across tasks, e.g., to seamlessly reuse supervision among related tasks or solve many tasks in one system without piling up the complexity. We proposes a fully computational approach for modeling the structure of space of visual tasks. This is done via finding (first and higher-order) transfer learning dependencies across a dictionary of twenty six 2D, 2.5D, 3D, and semantic tasks in a latent space. The product is a computational taxonomic map for task transfer learning. We study the consequences of this structure, e.g. nontrivial emerged relationships, and exploit them to reduce the demand for labeled data. For example, we show that the total number of labeled datapoints needed for solving a set of 10 tasks can be reduced by roughly 2 3 (compared to training independently) while keeping the performance nearly the same. We provide a set of tools for computing and probing this taxonomical structure including a solver that users can employ to devise efficient supervision policies for their use cases.