Browsing by Author "Falk, Martin Samuel"

Now showing 1 - 1 of 1

Open Access
Visualization and mesoscopic simulation in systems biology
(2013) Falk, Martin Samuel; Ertl, Thomas (Prof. Dr.)
A better understanding of the internal mechanisms and interplays within a single cell is key to the understanding of life. The focus of this thesis lies on the mechanism of cellular signal transduction, i.e. relaying a signal from outside the cell by different means of transport toward its target inside the cell. Besides experiments, understanding can also be achieved by numerical simulations of cellular behavior which require theoretical models to be designed and evaluated. This is where systems biology closely relates and depends on recent research results in computer science in order to deal with the modeling, the simulation, and the analysis of the computational results. Since a single cell can consist of billions of atoms, the simulation of intracellular processes requires a simplified, mesoscopic model. The simulation domain has to be three dimensional to consider the spatial, possibly asymmetric, intracellular architecture filled with individual particles representing signaling molecules. In contrast to continuous models defined by systems of partial differential equations, a particle-based model allows tracking individual molecules moving through the cell. The overall process of signal propagation usually requires between minutes and hours to complete, but the movement of molecules and the interactions between them have to be determined in the microsecond range. Hence, the computation of thousands of consecutive time steps is necessary, requiring several hours or even days of computational time for a non-parallel simulation. To speed up the simulation, the parallel hardware of current central processing units (CPUs) and graphics processing units (GPUs) can be employed. Finally, the resulting data has to be analyzed by domain experts and, therefore, has to be represented in meaningful ways. Typical prevalent analysis methods include the aggregation of the data in tables or simple 2D graph plots, sometimes 3D plots for continuous data. Despite the fact that techniques for interactive visualization of data in 3D are well-known, so far none of the methods have been applied to the biological context of single cell models and specialized visualizations fitted to the experts’ need are missing. Another issue is the hardware available to the domain experts that can be used for the task of visualizing the increasing amount of time-dependent data resulting from simulations. It is important that the visualization keeps up with the simulations to ensure that domain experts can still analyze their data sets. To deal with the massive amount of data to come, compute clusters will be necessary with specialized hardware dedicated to data visualization. It is, thus, important, to develop visualization algorithms for this dedicated hardware, which is currently available as GPU. In this thesis, the computational power of recent many-core architectures (CPUs and GPUs) is harnessed for both the simulation and the visualizations. Novel parallel algorithms are introduced to parallelize the spatio-temporal, mesoscopic particle simulation to fit the architectures of CPU and GPU in a similar way. Besides molecular diffusion, the simulation considers extracellular effects on the signal propagation as well as the import of molecules into the nucleus and a dynamic cytoskeleton. An extensive comparison between different configurations is performed leading to the conclusion that the usage of GPUs is not always beneficial. For the visual data analysis, novel interactive visualization techniques were developed to visualize the 3D simulation results. Existing glyph-based approaches are combined in a new way facilitating the visualization of the individual molecules in the interior of the cell as well as their trajectories. A novel implementation of the depth of field effect combined with additional depth cues and coloring aid the visual perception and reduce visual clutter. To obtain a continuous signal distribution from the discrete particles, techniques known from volume rendering are employed. The visualization of the underlying atomic structures provides new detailed insights and can be used for educational purposes besides showing the original data. A microscope-like visualization allows for the first time to generate images of synthetic data similar to images obtained in wet lab experiments. The simulation and the visualizations are merged into a prototypical framework, thereby supporting the domain expert during the different stages of model development, i.e. design, parallel simulation, and analysis. Although the proposed methods for both simulation and visualization were developed with the study of single-cell signal transduction processes in mind, they are also applicable to models consisting of several cells and other particle-based scenarios. Examples in this thesis include the diffusion of drugs into a tumor, the detection of protein cavities, and molecular dynamics data from laser ablation simulations, among others.