Searching for biological processes as targets for rheumatoid arthritis targeted therapy with ANDSystem, an integrated...

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized primarily by joint involvement with progressive destruction of cartilage and bone tissue. To date, RA remains an incurable disease that leads to a significant deterioration in quality of life and patient disability. Despite a wide arsenal of disease-modifying antirheumatic drugs, approximately 40 % of patients show an insufficient response to standard treatment, highlighting the urgent need to identify new pharmacological targets. The aim of this study was to search for novel biological processes that could serve as promising targets for the targeted therapy of RA. To achieve this goal, we employed an approach based on the automated extraction of knowledge from scientific publications and biomedical databases using the ANDSystem software. This approach involved the reconstruction and subsequent analysis of two types of associative gene networks: a) gene networks describing genes and proteins associated with the development of RA, and b) gene networks describing genes and proteins involved in the functional responses to drugs used for the disease's therapy. The analysis of the reconstructed networks identified 11 biological processes that play a significant role in the pathogenesis of RA but are not yet direct targets of existing disease-modifying antirheumatic drugs. The most promising of these, described by Gene Ontology terms, include: a) the Toll-like receptor signaling pathway; b) neutrophil activation; c) regulation of osteoblast differentiation; d) regulation of osteoclast differentiation; e) the prostaglandin biosynthetic process, and f) the canonical Wnt signaling pathway. The identified biological processes and their key regulators represent promising targets for the development of new drugs capable of improving the efficacy of RA therapy, particularly in patients resistant to existing treatments. The developed approach can also be successfully applied to the search for new targeted therapy targets for other diseases.