RECONSTRUCTION OF SCHIZOPHRENIA GENE NETWORK IN SEARCH FOR TARGET GENES

Abstract

Nowadays, schizophrenia is a poorly understood disease with a variety of symptoms attributed to other malconditions, and controversial diagnosis without well-defined treatment. Target therapy implies disease gene network reconstruction, gene clustering, identification of gene ontology categories and genes with the largest number of network contacts. The aim of the study is to analyze schizophrenia-associated genes, determine their position in the gene network, establish their correlation, identify key genes related to the disease, and evaluate them as target genes for drug therapy. Materials and Methods. The authors analyzed currently relevant data on schizophrenia using such online databases as OMIM, PANTHER, DAVID, GeneMANIA, STRING-DB, and GeneCards. They calculated categories of gene ontologies for 200 genes, such as biological processes, molecular functions and cellular compartments that reflect schizophrenia impact on the transmission of neuronal impulses. The authors also visualized and built gene networks containing the identified key objects and their interaction, identified the most relevant schizophrenia genes (COMT, DISC1, HTR2A, NRXN1) and a strongly connected cluster, including such genes as BDNF, SLC6A4, HTR2A, HTR2C, CHRM1, SRC, AKT, YWHAE, DISC1, DRD2, COMT, NDEL1, NOS1, CAMK28, etc. Results. The biological interpretation of the results obtained is still a great challenge, since schizophrenia is a genetically complex disease with numerous causes and triggering events. Analysis of schizophrenia-associated genes, and identification of their position in the gene network (connectivity) makes it possible to find out their interaction, determine the key genes of the disease, and evaluate their prospects as target genes for drug therapy.