Theoretical studies regarding the formation of the gene regulatory network optimal topology

This work presents the results of theoretical studies on the formation of the optimal topology of the gene regulatory network, which can be presented in the form of an oriented or unoriented graph. The topological parameters, the totality of which determines the network topology, are explored. It is shown that the nature of changes of various topological parameters in the process of network discharge can contradict each other, which complicates the process of network topology optimization. In this case, there is a need to find a compromise solution regarding the value of the thresholding coefficient, considering the optimal values of the number of network nodes and its connectivity. Diagrams, that are created, determine the nature of the distribution of the clustering coefficient of network nodes and the topological coefficient of the connectivity (degree) of the corresponding nodes. In this case, the complete HRM of patients studied for prostate cancer and included in the cancer genome atlas (TCGA - The Cancer Genome Atlas Program) is researched. The analysis of the resulting diagrams allows one to conclude that the nature of the dependence of the majority of genes that are directly or indirectly connected to each other (the main network) is non-linear and the value of both parameters sharply decreases at the initial stage of increasing the degree of nodes, and then the rate of change of the values of these parameters decreases significantly, when the value of connectivity (degree) increases. The values of both the clustering coefficient and the topological coefficient of nodes, that are not included in the main network, almost do not change when the degree of nodes increases. The ways of optimizing the topology of the gene regulatory network are determined, which involves the formation of the structure and topology of the network according to a group of single criteria, such as the clustering coefficient networks, network density, centralization coefficient and heterogeneity using a complex criterion containing separate criteria as components in the first stage. At the same time, the structure and topology of the network are formed by optimizing the corresponding threshold coefficient, which determines the presence or absence of connections between the corresponding nodes. At the second stage, the conformity of the network to the power law is assessed by analyzing the corresponding distributed parameters.

Further research prospects include the development of information technology for the reconstruction of gene regulatory networks for various types of gene expression data.

Keywords: gene expression, gene regulatory network, topological parameters, network topology optimization.

doi: 10.32403/0554-4866-2023-1-85-40-50