Method for modeling signal transduction in cells

• US 7,113,898 B2
• Filed: 11/07/2002
• Issued: 09/26/2006
• Est. Priority Date: 11/08/2001
• Status: Expired due to Fees

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Bisegna, Paolo, Andreucci, Daniele, DiBenedetto, Emmanuele
• Primary Examiner(s): PHAN, THAI Q
• Application Number:
  US10/289,880
• Publication Number:
  US 20030130828A1
• Time in Patent Office: 1,419 Days
• Field of Search: 703/2, 703/11, 703/12, 435/7.2, 435/23, 702/19, 382/128
• US Class Current: 703/2
• 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 5/30 Dynamic-time models

Abstract

The present invention provides a model that can be use to describe biological processes having a complex spatial geometry, for example, cell signaling processes. The models can also be used to model the pathology underlying diseases characterized by disrupted signaling pathways, and to identify target proteins at an appropriate site in a signal transduction network such that modulation of the target proteins elicits therapeutic effects. Methods of modeling diffusion processes, as well as machine-readable products embodying the methods are also disclosed.

Claims

1. A method of modeling a signal transduction pathway in a cell, the method comprising:

(a) determining a simulated geometry of a signaling pathway in a cell; and

(b) calculating spatial and temporal diffusion of a chemical species via the simulated geometry of the signal transduction pathway in the cell, whereby signal transduction in the cell is modeled.

2. The method of claim 1, wherein the cell is a vertebrate cell.

3. The method of claim 2, wherein the vertebrate cell is selected from the group consisting of a rod cell of an eye, a cone cell of an eye and a tumor cell.

4. The method of claim 1, wherein the simulated geometry is determined by employing one of homogenization theory and a concentrated capacity, and combinations thereof.

5. The method of claim 1, wherein the spatial and temporal diffusion of a chemical species comprises a coupled diffusion.

6. The method of claim 1, wherein the calculating comprises employing partial differential equations to describe the diffusion of the chemical species.

7. The method of claim 1, further comprising modeling signal transduction in a plurality of cells, whereby modeling of signal transduction in a tissue is accomplished.

8. A program storage device readable by a machine, tangibly embodying a virtual cell model produced by the method of any of claims 1–

6.

9. A program storage device readable by a machine, tangibly embodying a virtual tissue model produced by the method of claim 7.

10. The program storage device of claim 9, wherein the virtual tissue model is an eye model.

11. A program storage device readable by a machine, tangibly embodying a program of instructions executable by the machine to perform method steps for modeling a signal transduction pathway in a cell, the steps comprising:

(a) determining a simulated geometry of a signaling pathway in a cell; and

(b) calculating spatial and temporal diffusion of a chemical species via the simulated geometry of the signal transduction pathway in the cell, whereby a signal transduction pathway in the cell is modeled.

12. The program storage device of claim 11, wherein the cell is a cell of a vertebrate.

13. The program storage device of claim 12, wherein the cell is a rod cell of a vertebrate eye.

14. The program storage device of claim 11, wherein the simulated geometry is determined via homogenization theory, concentrated capacity, or combination thereof.

15. The program storage device of claim 11, wherein the spatial and temporal diffusion of a chemical species comprises a coupled diffusion.

16. The program storage device of claim 11, further comprising the step of modeling signal transduction in a plurality of cells, whereby modeling of signal transduction in a tissue is accomplished.

17. A method of modeling the diffusion of two or more entities in a medium, the method comprising:

(a) mathematically describing a medium;

(b) determining boundary source terms for two or more entities;

(c) expressing the diffusion of at least one of the two or more entities as a homogenized limit;

(d) expressing the diffusion of at least one of the two or more entities as a concentrated capacity limit; and

(e) calculating a spatial and temporal diffusion of one or more of the two or more entities by evaluating the homogenization limit and the surface evolution equation, whereby the diffusion of two or more entities in a medium is modeled.

18. The method of claim 17, wherein the medium is a cell.

19. The method of claim 18, wherein the medium is a rod outer segment.

20. The method of claim 17, wherein the expressing and the concentrating are by employing partial differential equations.

21. The method of claim 17, wherein the two or more entities are selected from the group consisting of cGMP, cGMP phosphodiesterase, activated cGMP phosphodiesterase, Ca²⁺, rhodopsin, activated rhodopsin, transducin and activated transducin.

22. The method of claim 17, wherein the boundary source terms are determined are determined for a species selected from the group consisting of Ca²⁺ and cGMP.

23. The method of claim 17, wherein the diffusion process is concentrated on the outer surface of a rod cell.

24. A program storage device readable by a machine, tangibly embodying a program of instructions executable by the machine to perform the method steps of any of claims 17–

23.

25. A program storage device readable by a machine, tangibly embodying a program of instructions executable by the machine to perform method steps for modeling diffusion of two or more entities in a medium, the steps comprising:

(a) mathematically describing a medium;

(b) determining boundary source terms for two or more entities;

(c) expressing the diffusion of at least one of the two or more entities as a homogenized limit;

(d) expressing the diffusion of at least one of the two or more entities as a concentrated capacity limit; and

(e) calculating a spatial and temporal diffusion of one or more of the two or more entities by evaluating the homogenization limit and the surface evolution equation, whereby the diffusion of two or more entities in a medium is modeled.

26. The program storage device of claim 25, wherein the medium is a cell.

27. The program storage device of claim 26, wherein the medium is a rod outer segment.

28. The program storage device of claim 25, wherein the expressing and the concentrating are by employing partial differential equations.

29. The program storage device of claim 25, wherein the two or more entities are selected from the group consisting of cGMP, cGMP phosphodiesterase, activated cGMP phosphodiesterase, Ca²⁺, rhodopsin, activated rhodopsin, transducin and activated transducin.

30. The program storage device of claim 25, wherein the boundary source terms are determined are determined for a species selected from the group consisting of Ca²⁺ and cGMP.

31. The program storage device of claim 25, wherein the diffusion process is concentrated on the outer surface of a rod cell.