jViz.RNA 4.0—Visualizing Pseudoknots and RNA Editing Employing Compressed Tree Graphs

Previously, we have introduced an improved version of jViz.RNA which enabled faster and more stable RNA visualization by employing compressed tree graphs. However, the new RNA representation and visualization method required a sophisticated mechanism of pseudoknot visualization. In this work, we present our novel pseudoknot classification and implementation of pseudoknot visualization in the context of the new RNA graph model. We then compare our approach with other RNA visualization software, and demonstrate jViz.RNA 4.0’s benefits compared to other software. Additionally, we introduce interactive editing functionality into jViz.RNA and demonstrate its benefits in exploring and building RNA structures. The results presented highlight the new high degree of utility jViz.RNA 4.0 now offers. Users are now able to visualize pseudoknotted RNA, manipulate the resulting automatic layouts to suit their individual needs, and change both positioning and connectivity of the RNA molecules examined. Care was taken to limit overlap between structural elements, particularly in the case of pseudoknots to ensure an intuitive and informative layout of the final RNA structure

Improving the portability and performance of jViz.RNA, a dynamic RNA visualization software

jViz.RNA is a Java based software that focuses on the visualization of RNA and its structural elements. It has been employed by many research groups around the world and has prompted excellent and constructive feedback from those groups, along with several suggestions for improvements. In this thesis, two major areas of jViz.RNA have been explored for the purpose of improvement; First, RNAML and FASTA file format support was added to jViz.RNA’s repertoire. This allows jViz.RNA users to utilize file formats used by other software, expanding jViz.RNA’s capabilities in working in pipeline systems, and also contributes to the standardization of RNA data exchange by supporting the use of RNAML. Second, five methods were explored in the context of improving the run time of jViz.RNA’s structure drawing algorithm. First, simple parameter optimization of the existing algorithm was attempted, then the use of the Barnes-Hut algorithm was explored, Thirdly, the effects of using multiple threads to handle the calculations were measured, additionally, the use of dynamic C libraries to integrate C code into the Java environment was investigated, and finally, a technique termed ’structure recall’, whereby the program uses files to register the layout of structures so they can be loaded for future runs, was examined. The results demonstrated that the use of approximation based techniques such as parameter optimization and the Barnes-Hut algorithm produces the most drastic improvements in run time, but does so at the cost of aesthetics, which may be unacceptable for visualization based software such as jViz.RNA. Multithreading and integration of C code, however, proved to be beneficial techniques since these improved the speed at which calculations are done, without distorting the structures in ways that obscure important information

jViz.RNA 4.0 - Advanced integration methods, pseudoknot visualization, and online editing in the context of RNA secondary structure visualization

RNA visualization software tools have traditionally presented a static visualization of RNA molecules with limited ability for users to interact with the resulting image once it is complete. Only a few tools allowed for dynamic structures; one such tool is jViz.RNA 2.0. Currently, jViz.RNA 2.0 employs a unique method for the creation of the RNA molecule layout by mapping the RNA nucleotides into vertexes in a graph, which we call the detailed graph, and then utilizes a Newtonian mechanics inspired system of forces to calculate a layout for the RNA molecule. The work presented here focuses on improvements to jViz.RNA 2.0 in four areas: First, the drawing of RNA secondary structures according to common drawing conventions employing a new underlying graph representation. Second, employing advanced numerical integration methods (the Backward Euler Method) to achieve dramatic run-time performance improvements utilizing the new graph implementation. Third, the ability to classify and visualize pseudoknots was added to jViz.RNA in order to extend the set of RNA structures that can be visualized. Finally, online base-pair removal and addition capabilities were incorporated into jViz.RNA in the interest of providing users with the capacity to modify, edit, and create RNA molecules from existing alternative representations (e.g. images or drawings). With regards to results, comparing the compressed graph and detailed graph implementations, it was found that the compressed graph produces results more consistent with RNA drawing conventions, and does so noticeably faster. Additionally, the advantages of the Backward Euler method as a more stable approach to mitigate interactions between users and the RNA model, allowing users to better and faster manipulate the RNA model, have been shown conclusively. The incorporation of pseudoknot visualization capacities demonstrated a new high degree of utility and flexibility since users are now able to visualize the majority, if not entirety, of biologically known RNAs, as well as modify the given pseudoknot representation. The implementation of online structure editing functionality allows users to construct related or theoretical molecules from existing ones, as well as construct arbitrary RNA structures from their primary nucleotide sequence

Numerical integration methods and layout improvements in the context of dynamic RNA visualization

Abstract Background RNA visualization software tools have traditionally presented a static visualization of RNA molecules with limited ability for users to interact with the resulting image once it is complete. Only a few tools allowed for dynamic structures. One such tool is jViz.RNA. Currently, jViz.RNA employs a unique method for the creation of the RNA molecule layout by mapping the RNA nucleotides into vertexes in a graph, which we call the detailed graph, and then utilizes a Newtonian mechanics inspired system of forces to calculate a layout for the RNA molecule. The work presented here focuses on improvements to jViz.RNA that allow the drawing of RNA secondary structures according to common drawing conventions, as well as dramatic run-time performance improvements. This is done first by presenting an alternative method for mapping the RNA molecule into a graph, which we call the compressed graph, and then employing advanced numerical integration methods for the compressed graph representation. Results Comparing the compressed graph and detailed graph implementations, we find that the compressed graph produces results more consistent with RNA drawing conventions. However, we also find that employing the compressed graph method requires a more sophisticated initial layout to produce visualizations that would require minimal user interference. Comparing the two numerical integration methods demonstrates the higher stability of the Backward Euler method, and its resulting ability to handle much larger time steps, a high priority feature for any software which entails user interaction. Conclusion The work in this manuscript presents the preferred use of compressed graphs to detailed ones, as well as the advantages of employing the Backward Euler method over the Forward Euler method. These improvements produce more stable as well as visually aesthetic representations of the RNA secondary structures. The results presented demonstrate that both the compressed graph representation, as well as the Backward Euler integrator, greatly enhance the run-time performance and usability. The newest iteration of jViz.RNA is available at https://jviz.cs.sfu.ca/download/download.html

Additional file 1 of Numerical integration methods and layout improvements in the context of dynamic RNA visualization

The file jViz3.0_Complete is a zip file containing a Java executable file (jViz3.0.jar), a User Manual in PDF format (jViz3.0 User Manual), and a subfolder containing RNA secondary structure files in.ct format for the RNA structures visualized in this manuscript (RNA_Structures). (ZIP 843 kb