Automated methods for simulating a biological network
First Claim
1. An automated method for simulating a developmental process of an organism, said method comprising:
- a) receiving initial condition values and process parameters for the developmental process of the organism;
b) representing the organism or a tissue within the organism by a graph data structure, wherein the graph data structure comprises;
i) a list of links, each link representing the interaction between two cells;
ii) a lineage tree recording the family tree of cell birth for the cells represented by the list of links; and
iii) a list of nodes, each node representing a cell of the cells represented by the list of links, with an embedding describing the location of the cell in Cartesian coordinates and a set of differential equations describing the time evolution of the location of the cell, said differential equations comprising the initial condition values and process parameters, each node comprising a model that comprises a system of differential equations and associated parameters describing the developmental process; and
c) repeatedly solving the set of differential equations in a series of steps for a defined number of steps, wherein after each step results are generated and compared to a threshold to determine whether the developmental process has reached a trigger point for changing the number of nodes in the list of nodes, thereby simulating the developmental process,wherein the developmental process is cell division, and wherein reaching the trigger point adds a new node to the list of nodes.
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Abstract
The present invention relates to methods, computer systems, and computer programs for simulating a biological network. The methods of the present invention facilitate biological network simulations via automated equation generation based on the concept of a hierarchy of canonical forms that describe biological processes at various levels of detail. At each level of hierarchy two classes of canonical forms can be identified: the input canonical form, that is used to supply information to the program, and the output canonical form that is produced by a simulator. The methods in certain preferred embodiments include explicit output description and flexible user intervention at several steps through the model generation. Furthermore, preferred embodiments of the present invention provide the modeling of developmental networks using an organism-as-a-graph approach using domains and fields.
36 Citations
10 Claims
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1. An automated method for simulating a developmental process of an organism, said method comprising:
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a) receiving initial condition values and process parameters for the developmental process of the organism; b) representing the organism or a tissue within the organism by a graph data structure, wherein the graph data structure comprises; i) a list of links, each link representing the interaction between two cells; ii) a lineage tree recording the family tree of cell birth for the cells represented by the list of links; and iii) a list of nodes, each node representing a cell of the cells represented by the list of links, with an embedding describing the location of the cell in Cartesian coordinates and a set of differential equations describing the time evolution of the location of the cell, said differential equations comprising the initial condition values and process parameters, each node comprising a model that comprises a system of differential equations and associated parameters describing the developmental process; and c) repeatedly solving the set of differential equations in a series of steps for a defined number of steps, wherein after each step results are generated and compared to a threshold to determine whether the developmental process has reached a trigger point for changing the number of nodes in the list of nodes, thereby simulating the developmental process, wherein the developmental process is cell division, and wherein reaching the trigger point adds a new node to the list of nodes. - View Dependent Claims (2, 3, 4, 5)
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6. An automated method for simulating a developmental process of an organism, said method comprising:
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a) receiving initial condition values and process parameters for the developmental process of the organism; b) representing the organism or a tissue within the organism by a graph data structure, wherein the graph data structure comprises; i) a list of links, each link representing the interaction between two cells; ii) a lineage tree recording the family tree of cell birth for the cells represented by the list of links; and iii) a list of nodes, each node representing a cell of the cells represented by the list of links, with an embedding describing the location of the cell in Cartesian coordinates and a set of differential equations describing the time evolution of the location of the cell, said differential equations comprising the initial condition values and process parameters, each node comprising a model that comprises a system of differential equations and associated parameters describing the developmental process; and c) repeatedly solving the set of differential equations in a series of steps for a defined number of steps, wherein after each step results are generated and compared to a threshold to determine whether the developmental process has reached a trigger point for changing the number of nodes in the list of nodes, thereby simulating the developmental process, wherein the developmental process is cell death, and wherein reaching the trigger point deletes a node from the list of nodes. - View Dependent Claims (7, 8, 9, 10)
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Specification