We propose to develop an open-source modeling environment, the Tissue-Simulation Environment (TSE), for the cell-based modeling of the structure and behavior of tissues and organs using the Cellular Potts Model (CPM) formalism. While groups worldwide have used the CPM methods to model biomedical phenomena, including vascular development, tumor growth, wound healing and the immune system, no open-source package currently supports this class of model.
Our Specific Aim i s that the TSE should provide modeling capability comparable to or better than other CPM simulations and be usable by and attractive to a broad community of biomodelers and experimentalists. To accomplish this aim we will provide a highly expandable core simulation engine, numerous validated sample biological models, a flexible and intuitive graphical user interface with visualization capability, extensive documentation and a number of modules describing biological processes not included in other CPM simulations. In addition we will provide user-training workshops and conduct ongoing user-need surveys. In response to the NIH Roadmap's call for interoperability and multiscale simulations, the TSE will also provide connectivity to other major subcellular and tissue-level software packages through a program of markup- language development and support. The TSE will also provide a mechanism to collect, validate and release user-submitted modules, models, bug reports and fixes to ensure that it develops rapidly and reliably in a way responsive to its users. Relevance: Simulations of cell interactions during embryonic development, wound healing, and disease can play an important role in experimental biomedical studies, help with the interpretation of experimental results, suggest experiments, predict experimental outcomes and lead to deeper understanding of fundamental biological mechanisms, thus expediting the understanding of diseases and the development of treatment strategies. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM077138-02
Application #
7502004
Study Section
Special Emphasis Panel (ZRG1-BST-D (51))
Program Officer
Lyster, Peter
Project Start
2007-09-28
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
2
Fiscal Year
2008
Total Cost
$513,174
Indirect Cost
Name
Indiana University Bloomington
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Somogyi, Endre; Glazier, James A (2017) A MODELING AND SIMULATION LANGUAGE FOR BIOLOGICAL CELLS WITH COUPLED MECHANICAL AND CHEMICAL PROCESSES. Symp Theory Model Simul 2017:
Belmonte, Julio M; Swat, Maciej H; Glazier, James A (2016) Filopodial-Tension Model of Convergent-Extension of Tissues. PLoS Comput Biol 12:e1004952
Somogyi, Endre; Sluka, James P; Glazier, James A (2016) Formalizing Knowledge in Multi-Scale Agent-Based Simulations. Model Driven Eng Lang Syst 16:115-122
de Almeida, Rita M C; Clendenon, Sherry G; Richards, William G et al. (2016) Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD. Hum Genomics 10:37
Clancy, Colleen E; An, Gary; Cannon, William R et al. (2016) Multiscale Modeling in the Clinic: Drug Design and Development. Ann Biomed Eng 44:2591-610
Somogyi, Endre; Hagar, Amit; Glazier, James A (2016) TOWARDS A MULTI-SCALE AGENT-BASED PROGRAMMING LANGUAGE METHODOLOGY. Proc Winter Simul Conf 2016:1230-1240
Wambaugh, John F; Wetmore, Barbara A; Pearce, Robert et al. (2015) Toxicokinetic Triage for Environmental Chemicals. Toxicol Sci 147:55-67
Thomas, Gilberto L; Belmonte, Julio M; Graner, François et al. (2015) 3D simulations of wet foam coarsening evidence a self similar growth regime. Colloids Surf A Physicochem Eng Asp 473:109-114
Somogyi, Endre T; Bouteiller, Jean-Marie; Glazier, James A et al. (2015) libRoadRunner: a high performance SBML simulation and analysis library. Bioinformatics 31:3315-21
Swat, Maciej H; Thomas, Gilberto L; Shirinifard, Abbas et al. (2015) Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D. PLoS One 10:e0127972

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