Method and apparatus for discovering target protein of targeted therapy

Patent metadata

Field	Value
Publication number	US-2016378911-A1
Application number	US-201615196656-A
Country	US
Kind code	A1
Filing date	Jun 29, 2016
Priority date	Jun 29, 2015
Publication date	Dec 29, 2016
Grant date	—

Abstract

An exemplary embodiment of the invention provides a discovery method of a protein which serves as a target of a target therapy, including: performing an attractor analysis on a first body signal transferring network of a cancer cell that is perturbed, and determining at least one of a plurality of proteins included in a third body signal transferring network of a cancer cell as a target protein based on the attractor analysis on the first body signal transferring network and an attractor analysis on a second body signal transferring network of a normal cell.

First claim

What is claimed is:

1 . A method of discovering a protein which serves as a target of a target therapy, the method comprising:
performing an attractor analysis on a first body signal transferring network of a perturbed cancer cell; and determining at least one of a plurality of proteins included in a third body signal transferring network of a cancer cell as a target protein based on the attractor analysis on the first body signal transferring network and an attractor analysis on a second body signal transferring network of a normal cell.

2 . The protein discovery method of claim 1 , wherein the performing the attractor analysis includes:
modeling the third body signal transferring network by applying a mutation map of a cancer state to the second body signal transferring network; modeling the first body signal transferring network by perturbing at least one of the plurality of proteins included in the third body signal transferring network; and simulating a signal-transmitting operation of the first body signal transferring network by using a Boolean network model.

3 . The protein discovery method of claim 2 , wherein the modeling of the first body signal transferring network includes modeling the first body signal transferring network by perturbing a combination of some of the plurality of proteins included in the third body signal transferring network.

4 . The protein discovery method of claim 2 , wherein the simulating the signal-transmitting operation includes:
determining the Boolean network model relating to a mutual relationship of proteins included in the first body signal transferring network; and time-dynamically simulating the first body signal transferring network based on the Boolean network model.

5 . The protein discovery method of claim 4 , wherein the simulating the signal-transmitting operation includes:
generating a truth table relating to the mutual relationship of the proteins included in the first body signal transferring network based on the Boolean network model; generating a state transition table showing state transition of the proteins based on the truth table; and determining an attractor indicating a final state of each protein included in the first body signal transferring network by generating a state transition diagram based on the state transition table.

6 . The protein discovery method of claim 1 , wherein the simulating the signal-transmitting operation includes calculating a basin size of an attractor of the perturbed cancer cell based on the simulation result of the first body signal transferring network.

7 . The protein discovery method of claim 6 , wherein the determining at the least one of the plurality of proteins included in the third body signal transferring network of the cancer cell as the target protein includes:
comparing a basin size of an abnormal one of attractors of the normal cell with a basin size of an abnormal one of attractors of the perturbed cancer cell; and, when a difference between the basin size of the abnormal one of the attractors of the normal cell with the basin size of the abnormal one of the attractors of the perturbed cancer cell is smaller than a predetermined value, determining at least one perturbed protein of the plurality of proteins included in the third body signal transferring network as the target protein.

8 . The protein discovery method of claim 6 , wherein the determining at the least one of the plurality of proteins included in the third body signal transferring network of the cancer cell as the target protein includes:
comparing a first basin size ratio of normal attractors and abnormal attractors among attractors of the normal cell with a second basin size ratio of normal attractors and abnormal attractors among attractors of the perturbed cancer cell; and, when a difference between the first basin size ratio and the second basin size ratio is smaller than a predetermined value, determining at least one perturbed protein of the plurality of proteins included in the third body signal transferring network as the target protein.

9 . The protein discovery method of claim 7 , wherein the determining the at least one perturbed protein of the plurality of proteins included in the third body signal transferring network as the target protein further includes, when at least two of the proteins included in the third body signal transferring network are the target protein, determining at least one of combinations of the at least two proteins as the target protein.

10 . The protein discovery method of claim 9 , wherein the determining the at the least one of combinations of the at least two proteins as the target protein includes,
when at least two of the proteins included in the third body signal transferring network are the target protein: generating a fourth body signal transferring network by making combinations of the at least two proteins and perturbing the combinations of the at least two proteins; and re-performing the attractor analysis on the fourth body signal transferring network.

11 . A discovery apparatus of a protein which serves as a target of a target therapy, the discovery apparatus comprising:
at least one processor; a memory; and a transceiver, wherein the at least one processor executes at least one program stored in the memory to perform: performing an attractor analysis on a first body signal transferring network of a perturbed cancer cell; and determining at least one of a plurality of proteins included in a third body signal transferring network of a cancer cell as a target protein based on the attractor analysis on the first body signal transferring network and an attractor analysis on a second body signal transferring network of a normal cell.

12 . The protein discovery apparatus of claim 11 , wherein the at least one processor performs:
modeling the third body signal transferring network by applying a mutation map of a cancer state to the second body signal transferring network; modeling the first body signal transferring network by perturbing at least one of the plurality of proteins included in the third body signal transferring network; and simulating a signal-transmitting operation of the first body signal transferring network by using a Boolean network model.

13 . The protein discovery apparatus of claim 12 , wherein the at least one processor, when performing the modeling of the first body signal transferring network, performs:
modeling the first body signal transferring network by perturbing a combination of some of the plurality of proteins included in the third body signal transferring network.

14 . The protein discovery apparatus of claim 12 , wherein the at least one processor, when performing the simulating of the signal-transmitting operation, performs:
determining the Boolean network model relating to a mutual relationship of the proteins included in the first body signal transferring network; and time-dynamically simulating the first body signal transferring network based on the Boolean network model.

15 . The protein discovery apparatus of claim 14 , wherein the at least one processor, when performing the time-dynamical simulating, performs:
generating a truth table relating to the mutual relationship of the proteins included in the first body signal transferring network based on the Boolean network model; generating a state transition table showing state transition of the proteins based on the truth table; and determining an attractor indicating a final state of each protein included in the first body signal transferring netw

Assignees

• Samsung Electronics Co Ltd
• Korea Advanced Inst Sci & Tech

Inventors

• Ha Misook
• Cho Kwang-Hyun
• Cho Sung-Hwan
• Park Sang-Min
• Lee Ho-Sung
• LEE Hwang-Yeol

Classifications

• G06F19/12 Primary

  Physics · mapped topic

• C40B30/02

  Chemistry & Metallurgy · mapped topic

• G06F19/28

  Physics · mapped topic

• G16B5/10 Primary

  Boolean models · CPC title

• G16B35/20

  Screening of libraries · CPC title