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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vavilov</journal-id><journal-title-group><journal-title xml:lang="ru">Вавиловский журнал генетики и селекции</journal-title><trans-title-group xml:lang="en"><trans-title>Vavilov Journal of Genetics and Breeding</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2500-3259</issn><publisher><publisher-name>Institute of Cytology and Genetics of Siberian Branch of the RAS</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18699/vjgb-26-11</article-id><article-id custom-type="elpub" pub-id-type="custom">vavilov-4975</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>БИОИНФОРМАТИКА И СИСТЕМНАЯ БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOINFORMATICS AND SYSTEMS BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Рациональный биоинформатический подход к анализу функциональных свойств метаболитов пробиотических микроорганизмов на основе реконструкции генных сетей</article-title><trans-title-group xml:lang="en"><trans-title>Rational bioinformatic approach to the analysis of functional properties of metabolites of probiotic microorganisms based on gene network reconstruction</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1859-4631</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванисенко</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanisenko</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><email xlink:type="simple">salix@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хлебодарова</surname><given-names>Т. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Khlebodarova</surname><given-names>T. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7537-2525</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Клещев</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kleshchev</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-8472-4945</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Волянская</surname><given-names>А. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Volyanskaya</surname><given-names>A. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-9245-8988</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Яцык</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Yatsyk</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-5923-3709</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Адамовская</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Adamovskaya</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0005-9155</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванисенко</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanisenko</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9433-8341</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Деменков</surname><given-names>П. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Demenkov</surname><given-names>P. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6800-8787</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колчанов</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolchanov</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новосибирск</p></bio><bio xml:lang="en"><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Курчатовский геномный центр ИЦиГ СО РАН<country>Россия</country></aff><aff xml:lang="en">Kurchatov Genomic Center of ICG SB RAS<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>05</day><month>03</month><year>2026</year></pub-date><volume>30</volume><issue>1</issue><fpage>5</fpage><lpage>14</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Иванисенко В.А., Хлебодарова Т.М., Клещев М.А., Волянская А.Р., Яцык И.В., Адамовская А.В., Иванисенко Т.В., Деменков П.С., Колчанов Н.А., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Иванисенко В.А., Хлебодарова Т.М., Клещев М.А., Волянская А.Р., Яцык И.В., Адамовская А.В., Иванисенко Т.В., Деменков П.С., Колчанов Н.А.</copyright-holder><copyright-holder xml:lang="en">Ivanisenko V.A., Khlebodarova T.M., Kleshchev M.A., Volyanskaya A.R., Yatsyk I.V., Adamovskaya A.V., Ivanisenko T.V., Demenkov P.S., Kolchanov N.A.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vavilov.elpub.ru/jour/article/view/4975">https://vavilov.elpub.ru/jour/article/view/4975</self-uri><abstract><p>Важное направление промышленной микробиологии – создание штаммов пробиотиков, обладающих ценными потребительскими свойствами. Индустрия пробиотиков является одним из наиболее динамично развивающихся сегментов пищевой и фармацевтической промышленности. Стеариновая (октадекановая) кислота C18:0 – один из основных метаболитов в клеточно-свободном супернатанте бактерии Streptococcus thermophilus, широко используемой в производстве различных ферментированных молочнокислых продуктов, включая йогурт и сыр. S. thermophilus влияет не только на текстуру и вкусовые свойства продуктов, но и обладает различными пробиотическими эффектами, в том числе антиоксидантной активностью, модуляцией кишечной микробиоты, ингибированием определенных патогенов и  др. Предполагается, что ряд пробиотических эффектов, которыми обладает S. thermophilus, может быть опосредован именно через октадекановую кислоту, как основной метаболит. Октадекановая кислота C18:0, как и другие длинноцепочечные жирные кислоты, поступает в организм человека с использованием различных механизмов белок-опосредованного транспорта и пассивной диффузии через мембрану клеток. В клетке стеариновая кислота не только служит субстратом для синтеза триглицеридов и других сложных липидов, но и, как показано на клеточных и in vivo моделях, является модулятором сигнальных и стресс-ответов, связанных в том числе с апоптозом. Это один из важных аспектов влияния стеариновой кислоты на функционирование организма, определяющий противовоспалительный и потенциально противоопухолевый эффекты. Однако молекулярно-генетические механизмы влияния октадекановой кислоты как пробиотика на организм человека в этом отношении остаются недостаточно изученными. В настоящем исследовании с помощью разработанной нами ранее информационно-программной системы ANDSystem, использующей методы машинного обучения и искусственного интеллекта и предназначенной для автоматического извлечения знаний из научных текстов и баз данных, были реконструированы генные сети регуляции внутреннего (митохондриального) и внешнего (индуцируемого рецепторами смерти) пути апоптоза клеток человека под влиянием стеариновой кислоты. Для поиска метаболитов, продуцируемых пробиотическими микроорганизмами, обладающих полезными терапевтическими свойствами, разработан новый поход, включающий реконструкцию генных сетей и анализ дифференциально экспрессирующихся генов. На его основе было показано, что стеариновая кислота, продуцируемая S. thermophilus, контролирует как внешний, так и внутренний пути апоптоза через регуляцию экспрессии гена PTGS2, кодирующего фермент циклооксигеназу-2. Полученные данные позволяют рассматривать циклооксигеназу-2 как один из центральных регуляторов, опосредующих влияние стеариновой кислоты на экспрессию генов апоптоза. В работе предложен рациональный биоинформатический подход к поиску новых штаммов, обладающих пробиотическим потенциалом, на основе оценки действия продуцируемых ими метаболитов на целевые биологические процессы в клетках человека через реконструкцию генных сетей.</p></abstract><trans-abstract xml:lang="en"><p>An important direction in industrial microbiology is the development of probiotic strains with valuable consumer properties. The probiotic industry is currently one of the most rapidly developing segments of the food and pharmaceutical sectors. Stearic (octadecanoic) acid C18:0 is one of the major metabolites present in the cell-free supernatant of the bacterium Streptococcus thermophilus, which is widely used in the production of fermented dairy products, including yogurt and cheese. S. thermophilus affects not only the texture and sensory properties of products, but also exhibits various probiotic effects, including antioxidant activity, modulation of the gut microbiota, inhibition of certain pathogens, and others. It is assumed that a number of probiotic effects exerted by S. thermophilus may be mediated through octadecanoic acid as one of its main metabolites. Octadecanoic acid C18:0, like other long-chain fatty acids, enters the human body via several mechanisms, including protein-mediated transport and passive diffusion across cell membranes. Inside the cell, octadecanoic acid serves not only as a substrate for the synthesis of triglycerides and other complex lipids, but, as shown in cell-based and in vivo models, also acts as a modulator of signaling and stress responses, including those associated with apoptosis. This is an important aspect of the influence of stearic acid on organism functioning, underpinning its anti-inflammatory and potentially anti-tumor effects. However, the molecular genetic mechanisms by which octadecanoic acid acts as a probiotic on the human organism remain insufficiently understood. In the present study, using our previously developed information – software system ANDSystem (employing machine learning and artificial intelligence for automatic extraction of knowledge from scientific texts and databases), we reconstructed gene networks regulating the intrinsic (mitochondrial) and extrinsic (death receptor-mediated) apoptotic pathways in human cells under the influence of stearic (octadecanoic) acid. To search for metabolites produced by probiotic microorganisms that may have beneficial therapeutic properties, we propose an approach that combines gene network reconstruction with differential gene expression analysis. Using this approach, we show that octadecanoic acid produced by S. thermophilus can control the intrinsic and extrinsic apoptotic pathways primarily via regulation of PTGS2 expression; the results indicate that cyclooxygenase-2 is a key regulator mediating the effect of octadecanoic acid on apoptosis-related genes.</p><p> </p></trans-abstract><kwd-group xml:lang="ru"><kwd>индустриальная микробиология</kwd><kwd>функциональные микроорганизмы</kwd><kwd>пробиотики</kwd><kwd>штаммыпродуценты</kwd><kwd>метаболиты</kwd><kwd>генные сети</kwd><kwd>ANDSystem</kwd></kwd-group><kwd-group xml:lang="en"><kwd>industrial microbiology</kwd><kwd>functional microorganisms</kwd><kwd>probiotics</kwd><kwd>producer strains</kwd><kwd>metabolites</kwd><kwd>gene networks</kwd><kwd>ANDSystem</kwd></kwd-group><funding-group xml:lang="ru"><funding-statement>This study was supported by the Ministry of Science and Higher Education of the Russian Federation (Federal Scientific and Technical Program for the Development of Genetic Technologies for 2019–2030), agreement No. 075-15-2025-516.</funding-statement></funding-group><funding-group xml:lang="en"><funding-statement>This study was supported by the Ministry of Science and Higher Education of the Russian Federation (Federal Scientific and Technical Program for the Development of Genetic Technologies for 2019–2030), agreement No. 075-15-2025-516.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Aardema H., van Tol H.T.A., Wubbolts R.W., Brouwers J.F.H.M., Gadella B.M., Roelen B.A.J. 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