Cetre Bioengineering RAS Moscow Physical Engineering Institure State

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

1. Introducing into the area of interest

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

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

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? 5

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 6

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

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

Importance of study 9

2. Problem statement

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

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 12

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

3. Simulation system

Levels of abstraction 15

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 16

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

Cell group structure • System’s main orientation is simulation of plant development 18

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

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

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

4. Program implementation

Operation steps 23

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

Extensibility • Multilevel architecture • Use of design patterns • Cross platform – Open. GL – MFC => wx. Widgets – Program core (most part of code) is platformindependent 25

5. Test results

Cell growth and division 27

Gene interaction loop with negative feedback 28

Genetic control of stem growth of Arabidopsis thaliana plant 29

HCV (hepatitis C virus) development and cell infection 30

6. Novelty

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 32

7. Conclusions

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

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

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

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