| 1. |
- Falk, Martin, et al.
(author)
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Parallelized Agent-based Simulation on CPU and Graphics Hardware for Spatial and Stochastic Models in Biology
- 2011
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In: Proceedings of the 9th International Conference on Computational Methods in Systems Biology, CMSB'112011. - New York, NY, USA : ACM Press. - 9781450308175 ; , s. 73-82
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Conference paper (peer-reviewed)abstract
- The complexity of biological systems is enormous, even when considering a single cell where a multitude of highly parallel and intertwined processes take place on the molecular level. This paper focuses on the parallel simulation of signal transduction processes within a cell carried out solely on the graphics processing unit (GPU). Each signaling molecule is represented by an agent performing a discretetime continuous-space random walk to model its diffusion through the cell. Since the interactions and reactions between the agents can be competitive and are interdependent, we propose spatial partitioning for the reaction detection to overcome the data dependencies in the parallel execution of reactions. In addition, we present a simple way to simulate the Michaelis-Menten kinetics in our particle-based method using a per-particle delay. We apply this agent-based simulation to model signal transduction in the MAPK (Mitogen-Activated Protein Kinase) cascade both with and without cytoskeletal filaments. Finally, we compare the speed-up of our GPU simulation with a parallelized CPU version resulting in a twelvefold speedup.
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| 2. |
- Falk, Martin, et al.
(author)
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3D Visualization of Concentrations from Stochastic Agent-based Signal Transduction Simulations
- 2010
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In: Biomedical Imaging: From Nano to Macro, 2010 IEEE International Symposium on. - : IEEE. - 9781424441259 - 9781424441266 ; , s. 1301-1304
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Conference paper (peer-reviewed)abstract
- Cellular signal transduction involves a transport step from the plasma membrane towards the nucleus, during which the signaling molecules are partly deactivated in control loops. This leads to a gradient in the concentration of active signaling molecules. The low number of molecules introduces spatio-temporal fluctuations and the asymmetric cellular architecture further increases the complexity. We propose a technique to represent this pattern in a continuous three-dimensional concentration map. The local concentration is computed and visualized with volume rendering techniques at interactive frame rates and is therefore well-suited for time-dependent data. Our approach allows the transition from the nano-scale of single and discrete signaling proteins to a continuous signal on the cell level. In the application context of this paper, we employ an agent-based Monte Carlo simulation to calculate the actual particle positions depending on reaction and transport parameters in the cell. The applicability of the proposed technique is demonstrated by an investigation of the effects of different transport parameters in Mitogen-activated protein kinase (MAPK) signaling.
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| 3. |
- Falk, Martin, et al.
(author)
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Visualization of Signal Transduction Processes in the Crowded Environment of the Cell
- 2009
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In: IEEE Pacific Visualization Symposium (PacificVis 2009). - 9781424444045 ; , s. 169-176
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Conference paper (peer-reviewed)abstract
- In this paper, we propose a stochastic simulation to model and analyze cellular signal transduction. The high number of objects in a simulation requires advanced visualization techniques: first to handle the large data sets, second to support the human perception in the crowded environment, and third to provide an interactive exploration tool. To adjust the state of the cell to an external signal, a specific set of signaling molecules transports the information to the nucleus deep inside the cell. There, key molecules regulate gene expression. In contrast to continuous ODE models we model all signaling molecules individually in a more realistic crowded and disordered environment. Beyond spatiotemporal concentration profiles our data describes the process on a mesoscopic, molecular level, allowing a detailed view of intracellular events. In our proposed schematic visualization individual molecules, their tracks, or reactions can be selected and brought into focus to highlight the signal transduction pathway. Segmentation, depth cues and depth of field are applied to reduce the visual complexity. We also provide a virtual microscope to display images for comparison with wet lab experiments. The method is applied to distinguish different transport modes of MAPK (mitogen-activated protein kinase) signaling molecules in a cell. In addition, we simulate the diffusion of drug molecules through the extracellular space of a solid tumor and visualize the challenges in cancer related therapeutic drug delivery.
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