Systems and methods for cell-centric simulation and cell-based models produced therefrom

A computer program product for modeling a biological event comprising a computer usable medium including a computer readable program, wherein the computer readable program when executed by a computer causes a method to be performed, the method comprising:

• receiving configurable simulation information;
• initializing an ontogeny engine to an initial step boundary in accordance with the configurable simulation information;
• advancing the ontogeny engine from a current step boundary to a next step boundary in accordance with the configurable simulation information and the current step boundary, the advancing comprising performing a stepCells function and a stepPhysics function;
• and
• continuing the advancing until a halting condition is encountered.

A system for modeling a biological event, comprising:

• a processor;
• a receive module configured to execute on the processor and receive configurable simulation information;
• an initialize module configured to execute on the processor and initialize an ontogeny engine to an initial step boundary in accordance with the configurable simulation information;
• an advance module configured to execute on the processor and advance the ontogeny engine from a current step boundary to a next step boundary in accordance with the configurable simulation information and the current step boundary, the advancing comprising performing a stepCells function and a stepPhysics function;
• and
• a halt detection module configured to execute on the processor and continue the execution of the advance module until a halting condition is encountered.

A computational component for directing one or more computing devices to model a biological event, the computational component comprising encoded computing device instructions emanating from a tangible computer readable medium, the encoded computing device instructions electronically accessible to at least one of the one or more computing devices for execution, the execution causing the one or more computing devices perform a method, the method comprising:

• receiving configurable simulation information;
• initializing an ontogeny engine to an initial step boundary in accordance with the configurable simulation information;
• advancing the ontogeny engine from a current step boundary to a next step boundary in accordance with the configurable simulation information and the current step boundary, the advancing comprising performing a killCells function, a stepCells function, a stepECM function and a stepPhysics function;
• and
• continuing the advancing until a halting condition is encountered.

A method for computer modeling development of a virtual multicellular tissue having an emergent property, the method comprising:

• assigning to a virtual cell, a heritable virtual genome containing a set of gene units, wherein each gene unit has a gene control region that specifies the activity of the gene unit in response to molecules in a virtual environment, and a structural region that specifies the type of molecule or molecules produced by the gene unit, and wherein the molecules produced by the set of gene units include at least one of (a1) an intercellular adhesion molecule, (a2) a cell division molecule, (a3) a cell growth molecule, (a4) an intercellular signaling molecule, and (a5) a cell differentiation molecule;
• assigning at least one of (b1) a chemical-interaction rule to govern the extra-genetic behavior of one or more molecules in virtual environment, (b2) an action rule to promote an adhesion, growth, or division condition of the virtual cell, and (b3) a physical-interaction rule to govern cell movement in response to one or more changes in the virtual environment,
• placing at least one virtual cell in the virtual environment;
• updating the state of the virtual cell in the virtual environment, wherein updating includes
• refreshing the status of molecules produced by the set of gene units in the virtual cell;
• applying the chemical-interaction rule to update the status of the molecules present in the virtual cell and, optionally, in the virtual environment;
• applying the action rule to update the adhesions, growth, and division actions taken by the virtual cell;
• and
• applying the physical-interaction rule to update the position of the virtual cell with respect to the virtual environment;
• and
• repeating the updating step until a virtual multicellular tissue having one or more desired emergent properties develops.

A computer-implemented method of modeling epithelial tissue growth comprising:

• receiving configurable simulation information, the configurable simulation information including:
• configured physical and chemical parameters;
• configured environmental information;
• configured metabolic information;
• initializing an ontogeny engine to an initial step boundary in accordance with the configurable simulation information, wherein the initial step boundary defines at least one virtual stem cell in a virtual environment;
• advancing the ontogeny engine from a current step boundary to a next step boundary in accordance with the configurable simulation information and the current step boundary, the advancing comprising performing a stepCells function, a stepECM function, and a stepPhysics function;
• and
• continuing the advancing until a halting condition is encountered.

A multi-cellular virtual tissue having the emergent properties of self-repair, adaptive response to an altered environment, or tissue differentiation, comprising

• (a) a plurality of virtual cells, each having a heritable virtual genome containing a set of virtual genes, each virtual gene having a gene-control region that specifies the activity of the virtual gene in response to virtual molecules in the virtual environment, and a structural region that specifies the type of molecule or molecules produced by the virtual gene, wherein the molecules produced by the genes include at least one related to each of (a1) intercellular adhesion, (a2) cell division, (a3) cell growth, (a4) intercellular signaling, and (a5) cell differentiation;
• wherein
• (b) the operation and actions of the virtual genes are guided by (b1) chemical-interaction rules that govern the extra-genetic behavior of one or more molecules placed or produced in the virtual cells or in the extra-cellular environment of the cells, (b2) action rules that specify a cell's adhesion, growth, or division condition, in response to one or more molecules produced by a cell's gene(s) relating to intercellular adhesion, cell growth, or cell division, respectively, and (b3) physical-interaction rules that govern how a cell will move in response to its own growth or division or the growth or division of neighboring cells;
• and wherein
• (c) the tissue is produced by iteratively updating the state of each cell by applying the gene control and molecule production, chemical-interaction rules, action rules, and physical-interaction rules to the existing state of each virtual cell.