• Research











    • CellSim

    CellSim is a Free Software (GPL) "cell simulator" package that we are developing in our group to accurately model complex signaling or metabolic networks within both arbitrary shaped heterogeneous, multi-compartment cells or homogeneous or "well mixed" cells.

    The program can take an arbitrary number of reactions (defined by a simple text based input file) with arbitrary spatial geometry) and generate automatically the appropriate coupled set of ODE/PDEs that govern transport both within compartments and between compartments (based on the overlap between compartments).

    We have attempted to keep the codebase as modular as possible to provide easy extensibility and are currently using the code base to analyze a variety of systems, most recently the MAPK signaling pathway.

    The mathematics underlying CellSim are simply reaction-diffusion equations based with appropriate, biologically relevant, boundary conditions within compartments.

    Currently, the code is going through a large degree of flux as the project and features are being added as we speak. Source and binaries are provided under the Gnu Public License. We have CVS access available if you want our cutting edge betas. Drop an email if interested.

    A highlight of the features (some we are still working on) include :

    • Highly optimized, modular, portable C++ codebase.
    • pseudo-C scripting language (work in progress)
    • Unified code has both single processor and multiprocessor (MPI) enabled features.
      • Multiprocessor calculations scales linearly with grid size
      • Parameter optimization features scale linearly.
    • Arbitrary geometry and arbitrary compartmental interactions
    • multiple "reaction" integration schemes including:
      • Euler
      • 2nd Order Runge Kutta
      • 4th Order Runge Kutta
      • Exponential Euler
      • Adaptive 4th Order Runge Kutta
      • 4th order Rosenbrock
    • multiple "diffusion" integration schemes
      • Dufort-Frankel
      • FTCS
      • Diffusion constants tagged by species, location or globally
    • Kinetics and Diffusion are coupled using Strang splitting, adaptive Rosenbrock-FTCS reaction-diffusion integrator is available (beta)
    • Oncogene Explorer (currently script based)
    • Sensitivity Analysis Module
      • Automated fast generation and calculation of hessian for use with Rosenbrock Integrators (forward differentiation takes advantage of sparsity)
      • Generalization of Sensitivity Analysis to spatio-temporal realm (work in progress) B
    • Metabolic Control Analysis Module currently "functional relationships" only (i.e. no flux relationships)
      • Automated generation of conservation relationships
    • Client/server model with CellSimVis : Connects/controls numerical backend through the network (work in progress)
    • Parameter optimization Module
      • Both Multiple/Single experiment, multiple global parameter fitting
      • Arbitrary assignment of subset of parameters to subset of available experiments for optimization.
      • Optimization routines currently available :
        • Simulated Annealing
        • We are working on using global optimization procedures taken from the protein folding community and applying them to this problem.
    Projected Features
    • Extend underlying reaction model to applications in other areas (ie. mathematical biology, nonlinear dynamics, atmospheric science)



    CellSim Vis

    CellSim Vis is the current incarnation of CellSim's graphical front-end. Still in early development, CellSim Vis will handle all aspects of CellSim simulations -- from creation, through execution, to visualization. We have chosen to develop CellSim Vis using Trolltech's Qt widget set, and the software's visualization tools rely heavily on OpenGL 3D graphics libraries.
    • Current Features
      • Concentration-time series plotting of all points on any 1,2, or 3D rectangular grid
      • 2D/3D time lapse contour plots of 2D grids
      • Mouse-based interactive image manipulation: zoom, "trackball" rotation, scaling
      • Reads files in native CellSim plotting format (ascii-based)
      • Reads/displays CellSim data received over remote socket connections (beta)
      • Flexible, modular design
    • Projected Features
      • Point and click graphical creation of biological pathways, grid geometry, initial parameters, and control
      • Automated job submission
      • Realtime, interactive data visualization with CellSim using client-server model
      • 3D time lapse contour plots of 3D grids

    Systems Biology

    Please visit our newly developed Systems Biology of The Cell Initiative being developed by a group of faculty members (including me) here at Drexel University.

    Neuroreceptor Pathways

    We have recently been examining the neuroreceptor pathways with specific focuses on the nicotinic acetylcholine receptor, the serotonin receptors and the two main classes of dopamine receptors.

    An overview of the complex interactions that make up these neuroreceptor pathways may be found here. We have connected several pathways of interest into this map including the MAPK pathway

    Cell Damage and Shock

    We have recently also been examining how systems models may be used to examine how cells respond to growth factors (EGF), stress, osmotic shock, inflammation and radiation. An overview of these pathways and the careful balance between apoptisis and cell survival can be found here.

    Philadelphia Biophysics Colloquia

    A list of interesting Colloquium going on through out the philadelphia region is available here. The list is currently being filled in primarily through Angie Young's Biophysics Colloquium list for the University of Pennsylvania and Drexel Univerity's Physics Department. Drop me an email and I can add any individual talks or a departmental seminar series.

    User Manual

    We have recently made a manual for the usage of CellSim

    Would you like to be part of our group?

    Take a look at this presentation (in pdf format) for a quick rundown of the many great things that are otherwise known as the Physics of Biophysics!

    Downloads

    You may download the CellSim code from it CVS repository. The repository is on bio.physics.drexel.edu. Instructions for downloading and compiling are available in our User Manual
    Please send comments and suggestions to avijit@physics.drexel.edu

    • Supplemental Material for "Automated Oncogene Detection in Complex Protein Networks with Applications to the MAPK Signal Transduction Pathway,"