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# Frequently Asked Questions (FAQ)

## What is a gene network?

Gene network is a group of coordinately expressed genes controlling a particular function of an organism. A gene network consists of several types of components:

• the gene network nucleus composed by a group of genes mentioned above;
• proteins encoded by these genes;
• signal transduction pathways providing activation or suppression of gene expression;
• negative and positive feedback stabilizing parameters of a gene network at particular level, or on the contrary, deviating these parameters from the starting value, thus providing transition of a gene network to the novel functional condition;
• low molecular components switching the gene network functioning in response to external stimuli (hormones and other signal molecules), energy components, metabolites, etc.

## What are mathematical and computer models of a gene network?

As a mathematical model, we understand the formalized description of the gene network functioning given in terms of some mathematical language.

Under computer model of a gene network, we understand the complex of algorithms and programs, calculating the dynamic characteristics of gene network on the base of mathematical models, in accordance with the ordered initial data.

In the current release, the mathematical models are given in terms of systems of autonomous common differential equations presenting the laws of alteration of concentration rates of biomolecules and their complexes (genes, mRNAs, proteins, enzymes, low molecular compounds, the products of interaction between them, etc.), which are essential for the gene network functioning. The models are constructed within the frames of the generalized chemical kinetic simulation method (GCKSM) and may be referred to the portrait type.

## What is the method applied for the gene network modeling?

For gene network modeling, the generalized chemical kinetic simulation method (GCKSM) is applied.

## What is the generalized chemical kinetic simulation method (GCKSM)?

The generalized chemical kinetic simulation method (GCKSM) is oriented to the formalized, mainly portrait, description of regularities in functioning of an arbitrary biosystem. [Bazhan S.I., Likoshvai V.A., Belova O.E. (1995) Theoretical analysis of the regulation of interferon expression during priming and blocking. J. Theor. Biol., 175, 149-160.].

Formalizaton in the GCKSM is performed according to a block principle. Due to this principle, a system simulated is divided into elementary subsystems, each of these subsystems being described individually. Description of elementary subsystems is made in terms of formal blocks. The synthesis of models out from elementary subsystems is provided according to the principle of summing the rates of elementary processes.

## What is an elementary subsystem?

Elementary subsystem is a part of biosystem that can be described independently from the other parts.

## What is a formal block?

In GCKSM, a formal block means a construction, isolated into a separate unit. This construction is uniquely characterized by an ordered list of formal dynamic variables , ordered list of formal parameters , and the law of transformation of information . When the formal block is used, its formal dynamic variables and parameters are supplied by the definite values. An elementary process is the formal block used in a model. Within the frames of the GCKSM, the elementary subsystems of biosystems are described by the aggregate of elementary processes. Five types of formal blocks may be used for construction of gene network models, namely: constitutive synthesis, monomolecular reaction, bimolecular reaction, generalized Michaelis-Menten reaction of the type 1, generalized Michaelis-Menten reaction of the type 2.

## What is the principle of summing the rates of elementary processes?

In elementary processes, described by application of five types of formal blocks, the actual variables have the sense of concentrations of definite biomolecules. The law of transformation of information orders the rates of alterations of these concentrations in a process given. Then, following the principle of summing, the total rate of alteration of concentration of a biomolecule equals to the sum of rates of its alteration throughout all elementary processes.

## Where the mathematical models of gene networks are being developed?

Mathematical models of gene networks are being developed in the Laboratory of Theoretical Genetics and in the Sector of Molecular Evolution of the Institute of Cytology and Genetics SB RAS.

## Where the mathematical models of gene networks are installed?

Mathematical models of gene networks are installed in the GeneNet database.

## Mathematical models of which gene networks have been developed?

Currently, the mathematical models of dynamics of the following two gene networks have been developed:

## What numerical calculations could be done by mathematical models?

By means of mathematical models, it is possible to produce the following operations:

1) Numerical simulation of dynamical characteristics of biological systems under very different conditions, such as:

• viewing the reaction of a gene network in response to alteration of initial concentration values of the system’s components;
• viewing the reaction of a gene network in response to alteration of the values of concentrations of the system’s components under the fixed time periods;
• viewing the gene network behavior in response to alteration of parameters determining the rates of elementary processes;
• computer simulation of gene mutation (disruption of gene or enzyme function, alteration of rates of translation, transcription, transportation, utilization processes, etc.) by varying the parameters of a gene network mathematical model.

2) Comparative analysis of numerical data obtained theoretically to experimental data.

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