vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-107vavilov-4885Research ArticleСИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯSYSTEMS COMPUTATIONAL BIOLOGYПрименение программно-информационной системы AND-System для поиска мишеней таргетной терапии ревматоидного артрита на основе анализа биологических процессовSearching for biological processes as targets for rheumatoid arthritis targeted therapy with AND-System, an integrated software and information platformМищенкоЕ. Л.MishchenkoE. L.

Новосибирск

Novosibirsk

https://orcid.org/0009-0001-9245-8988ЯцыкИ. В.YatsykI. V.

Новосибирск

Novosibirsk

woikin88@mail.ruhttps://orcid.org/0000-0001-9433-8341ДеменковП. С.DemenkovP. S.

Новосибирск

Novosibirsk

https://orcid.org/0009-0002-5923-3709АдамовскаяА. В.AdamovskayaA. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-0005-9155ИванисенкоТ. В.IvanisenkoT. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-7537-2525КлещевМ. А.KleshchevM. A.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-1859-4631ИванисенкоВ. А.IvanisenkoV. A.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian Federation20251212202529710201030Copyright © Мищенко Е.Л., Яцык И.В., Деменков П.С., Адамовская А.В., Иванисенко Т.В., Клещев М.А., Иванисенко В.А., 20252025Мищенко Е.Л., Яцык И.В., Деменков П.С., Адамовская А.В., Иванисенко Т.В., Клещев М.А., Иванисенко В.А.Mishchenko E.L., Yatsyk I.V., Demenkov P.S., Adamovskaya A.V., Ivanisenko T.V., Kleshchev M.A., Ivanisenko V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4885

   Ревматоидный артрит (РА) – системное аутоиммунное заболевание, сопровождающееся поражением преимущественно суставов с прогрессирующей деструкцией хрящевой и костной тканей. До настоящего времени РА остается неизлечимым заболеванием, приводящим к значительному ухудшению качества жизни и инвалидизации пациентов. Несмотря на наличие широкого арсенала базисных противовоспалительных препаратов, около 40 % пациентов демонстрируют недостаточный ответ на стандартное лечение, что подчеркивает острую необходимость поиска новых фармакологических мишеней.

   Целью настоящей работы был поиск новых биологических процессов, которые могут служить перспективными мишенями для таргетной терапии РА.

   Для достижения поставленной цели был применен подход, основанный на автоматическом извлечении знаний из текстов научных публикаций и биомедицинских баз данных с помощью программно-информационной системы AND-System. Данный подход включал реконструкцию и последующий анализ ассоциативных генных сетей двух типов: а) генные сети, описывающие гены и белки, ассоциированные с развитием РА, и б) генные сети, описывающие гены и белки, вовлеченные в функциональные ответы на действие лекарств, применяемых для терапии заболевания. В результате анализа реконструированных сетей выявлено 11 биологических процессов, играющих значимую роль в патогенезе ревматоидного артрита, но до сих пор не являющихся прямыми мишенями существующих базисных противовоспалительных препаратов. К числу наиболее перспективных относятся следующие процессы, описываемые терминами онтологии генов: а) сигнальный путь Toll-подобных рецепторов; б) активация нейтрофилов; в) регуляция дифференцировки остеобластов; г) регуляция дифференцировки остеокластов; д) биосинтез простагландинов; е) канонический сигнальный путь Wnt. Выявленные биологические процессы и их ключевые регуляторы представляют собой перспективные мишени для разработки новых лекарственных средств, способных повысить эффективность терапии РА, в том числе у пациентов, резистентных к существующим методам лечения. Разработанный подход может быть успешно использован для поиска новых мишеней таргетной терапии и при других заболеваниях.

   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.

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The authors declare that there are no conflicts of interest present.