Simulating genes operation and interaction Rekubratsky V.A., Korotkova M.A. Cetre Bioengineering RAS Moscow Physical Engineering Institure (State University)

1. Introducing into the area of interest

3 Basic concepts 1.Gene 2.Gene operation 3.Genes interaction 4.Gene network 5.Gene network representation

4 1. Gene Hereditary (inheritance) information unit Defines every organism development What does genes operation mean?

5 2. Gene operation (gene activity) Responsible for producing its special protein Protein amount is the characteristic that can be measured Production rate varies from cell to cell What does it depend on?

6 3. Genes interaction Some proteins can have positive or negative influence on production rates of other proteins This is the way genes can interact with each other May occur within one cell or throughout a part of organism

7 4. Gene network System of gene interactions Usually represented by a directed graph: –Vertices represent genes –Arcs represent interaction facts

8 5. Gene network representation gene B activates gene A (positive interaction) gene B suppresses gene A (negative interaction) Real network exampleElementary interactions

9 Importance of study

2. Problem statement

11 Problems of gene network representation No dynamics No cell localization of interaction processes Hard to test Hard to verify conformity with experimental data

12 Computer simulation system to be designed: Simulates genes operation and interaction in a multicellular organism basing on gene network graph Thus verifies conformity with experimental data

13 Computer simulation system to be designed: Takes cell localization of interaction processes into consideration Enables explicit manipulation of gene operation

3. Simulation system

15 Levels of abstraction

16 Gene model Outer state – amount of protein Inner state – protein generation ability Speed of protein degradation (gradual decrease of protein amount) Block flag – to manipulate gene operation explicitly

17 Universal mechanism of describing both vital activity and interaction processes Interaction rules

18 Cell group structure Systems main orientation is simulation of plant development

19 Cell group structure Hemisphere structure is an approximation to plants cell group giving birth to the whole upper part of plant

20 Cell group structure However, the structure can be used for simulation of many other vital processes in different organisms

21 Simulation flow Step-by-step Each step corresponds to one cell group state: –cell group structure –cell parameters –gene parameters

4. Program implementation

23 Operation steps

24 Interface tendencies Simplification: –Network creation similar to common drawing –Use of algebraic notation in interaction rule expressions Visual aids –3D model of cell structure –Graphical indication of simulation flow details –Graphs for cell and gene parameters

25 Extensibility Multilevel architecture Use of design patterns Cross platform –OpenGL –MFC => wxWidgets –Program core (most part of code) is platform- independent

5. Test results

27 Cell growth and division

28 Gene interaction loop with negative feedback

29 Genetic control of stem growth of Arabidopsis thaliana plant

30 HCV (hepatitis C virus) development and cell infection

6. Novelty

32 System advantages comparing to analogs For gene network simulation : –takes cell localization of interaction processes into consideration For all-purpose simulation: –a simpler interface, does not demand programming skills from a user

7. Conclusions

34 System demonstrates: Adequacy to simulate gene network operation in multicellular structures Universality to describe large variety of cell interaction and vital activity processes

35 Perspectives and plans Development of approaches and algorithms to solve inverse problem Transformation into totally cross-platform system Further interface simplification

The work is supported by Science & Technology International Park Technopark in Moskvorechje along with UMNIK program

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