Hierarchical biological modelling system and method

• US 5,808,918 A
• Filed: 06/25/1997
• Issued: 09/15/1998
• Est. Priority Date: 04/14/1995
• Status: Expired due to Term

• Current Assignee: Entelos Holding Corp. (SilkRoad Inc.)
• Original Assignee: Medical & Scientific Sensors
• Inventors: Kornman, Kenneth S., Fink, Pamela K.
• Primary Examiner(s): Teska, Kevin J.
• Assistant Examiner(s): Walker, Tyrone V.
• Application Number:
  US08/882,597
• Time in Patent Office: 447 Days
• Field of Search: 364/578, 364/496, 364/554, 364/499, 364/500, 707/3, 395/920
• US Class Current: 703/11
• CPC Class Codes: C07K 1/00 General methods for the preparation of peptides , i.e. processes for the organic chemical preparation of peptides or proteins of any length
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16B 5/20 Probabilistic models
• CPC Class Codes: G16B 5/30 Dynamic-time models
• CPC Class Codes: G16C 20/10 Analysis or design of chemical reactions, syntheses or processes
• CPC Class Codes: G16H 10/20 for electronic clinical trials or questionnaires
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: G16H 70/60 relating to pathologies

Abstract

A hierarchical biological modelling system and method provides integrated levels of information synthesized from multiple sources. An executable model of a biological system is developed from information and structures based on the multiple sources. The model is balanced to ensure that it matches the information and structures. Once the model is created and balanced it can be used to provide insight into phenomena at the cellular, or subcellular level, as well as phenomena at the patient, organ and system levels. From this information clinical trials can be emulated, biologic targets for drug development can be identified and subcellular phenomena over time can be observed. The model provides an integrated view of a multi-variable biological system.

Claims

1. A computer executable model of a hierarchical biological system, the model for use with a computer system including a memory and a processor, the model comprising:

a plurality of biological modelling units stored in the memory, each biological modelling unit having;

a plurality of chemical level inputs, each input representing a level of a chemical in an environment containing the biological modelling unit;

at least one chemical production output representing a level of a chemical produced by the biological modelling unit and stored as part of the environment containing the biological modelling unit; and

a chemical production function describing the production output of a chemical by the biological modelling unit as a function of the chemical level inputs; and

the plurality of biological modelling units organized into a plurality of levels, each level representing a different level of biological function, each biological modelling unit in any level providing its chemical production outputs to the environment containing the biological modelling unit, receiving as its chemical level input, chemical levels from the environment, and wherein execution of the model by the processor modifies the respective inputs and outputs of each of the biological modelling units.

2. The computer executable model of claim 1, further comprising:

a regulator biological modelling unit representing a regulator function comprising;

at least one chemical level input representing a level of a chemical in an environment containing the regulator biological modelling unit;

at least one quantity input representing a quantity of a first type of biological modelling unit in the environment; and

a regulator function describing a change in state of the first type of biological modelling unit to a second type of biological modelling unit as a function of the chemical level and quantity inputs, wherein execution of the model by the processor causes respective changes in the quantities of the first and second types of biological modelling units.

3. The computer executable model of claim 1, wherein first and second biological modelling units represent first and second cell pools, each cell pool representing cells of a particular type or cells in particular state, the model further comprising:

a regulator biological modelling unit representing a regulator function comprising;

at least one chemical level input representing a level of a chemical in an environment containing the regulator biological modelling unit;

at least one quantity input representing a quantity of a first type of biological modelling unit in the environment; and

regulator function describing a change in state of the first type of biological modelling unit to a second type of biological modelling unit as a function of the chemical level and quantity inputs, wherein execution of the model by the processor causes respective changes in the quantities of the first and second types of biological modelling units, and representing changes in the quantities of cells in the respective first and second cell pools.

4. A computer executable model of a hierarchical biological system, the model for use with a computer system including a memory and a processor, the model comprising:

a plurality of cell pool modelling units stored in the memory, each cell pool modelling unit representing a quantity of a cells having a particular cell type or a particular cell state, each cell type modelling unit having;

at least one chemical level input representing a level of a chemical in an environment containing the cell pool modelling unit;

at least one quantity input representing a quantity of a cells of a selected cell pool modelling unit; and

at least one chemical production function, executable by the processor, that outputs a level of a chemical produced by the cell pool modelling unit in response to the chemical level input and quantity input;

wherein execution of the model by the processor causes the chemical production function of each cell pool modelling unit to modify the output of the level of chemical of produced by the cell pool modelling unit; and

a plurality of regulator modelling units stored in the memory, each regulator modelling unit associated with selected first and second cell pool modelling units, and having;

at least one input of either;

a level of a chemical in the environment of the first cell pool modelling unit;

or

a quantity of a cell in the environment of the first cell pool modelling unit; and

a regulator function, executable by the processor, and representing the transition of cells between the first and second cell pool modelling units by modifying the quantity of the cells represented by the first cell pool modelling unit and the quantity of cells represented by the second cell pool modelling unit; and

wherein execution of the model by the processor causes each regulation function to dynamically modify the quantity of cells represented by each cell pool modelling unit.

5. A computer executable model of a hierarchical biological system, the model for use with a computer system including a memory and a processor, the model comprising:

a plurality of cell pool modelling units stored in the memory, each cell pool modelling unit representing a quantity of cells of a particular type of cell or a particular cell state and having a chemical production function describing an output level of a chemical produced by the cells of the cell pool modelling unit as a function of either a quantity of cells of at least one cell pool modelling or a level of a chemical;

a plurality of cell pool regulator functions, stored in the memory and executable by the processor, each cell pool regulator function regulating the quantities of cells associated with selected ones of the cell pool modelling units in response to inputs including at least one of a level of a chemical in an environment containing the cell pool modelling units or a quantity of cells represented by a cell pool modelling unit;

a plurality of a cell class modelling units stored in the memory, each cell class modelling unit associated with selected ones of the cell pool modelling units and selected ones of the cell pool regulator functions, and representing the biological functions of a single class of cells;

a plurality of system modelling units stored in the memory, each system modelling unit associated with selected ones of the cell class modelling units, and representing a coordinated biological function of an anatomic system; and

wherein execution of the model causes the chemical production functions of the cell pool modelling units to dynamically modify the levels of chemical produced by the cell pool modelling units, and causes the cell pool regulator functions to dynamically modify the quantities of cells represented by the cell pool modelling units.