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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-24-96</article-id><article-id custom-type="elpub" pub-id-type="custom">vavilov-4410</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>СИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>SYSTEMS COMPUTATIONAL BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Изучение особенностей метаболизма тканей глиобластомы и перитуморального пространства при использовании таргетированного метаболомного скрининга методом ВЭЖХ-МС/МС и генных сетей</article-title><trans-title-group xml:lang="en"><trans-title>Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Басов</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Basov</surname><given-names>N. V.</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">basov@nioch.nsc.ru</email><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-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3338-8529</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рогачев</surname><given-names>А. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Rogachev</surname><given-names>A. D.</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"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гайслер</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Gaisler</surname><given-names>E. 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-3"/></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-2"/></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-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вензель</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Venzel</surname><given-names>A. 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-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0903-7278</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мишинов</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Mishinov</surname><given-names>S. 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-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ступак</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Stupak</surname><given-names>V. 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-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чересиз</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Cheresiz</surname><given-names>S. 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-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Олешко</surname><given-names>О. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Oleshko</surname><given-names>O. 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-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бутикова</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Butikova</surname><given-names>E. 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-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0007-5841-9567</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Осечкова</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Osechkova</surname><given-names>A. E.</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-6"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сотникова</surname><given-names>Ю. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Sotnikova</surname><given-names>Yu. 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-7"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Патрушев</surname><given-names>Ю. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Patrushev</surname><given-names>Y. 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-8"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Поздняков</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Pozdnyakov</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Иркутск</p></bio><bio xml:lang="en"><p>Irkutsk</p></bio><xref ref-type="aff" rid="aff-9"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лаврик</surname><given-names>И. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Lavrik</surname><given-names>I. N.</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-10"/></contrib><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><xref ref-type="aff" rid="aff-11"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5982-8580</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Покровский</surname><given-names>А. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Pokrovsky</surname><given-names>A. G.</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-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук;&#13;
Новосибирский национальный исследовательский государственный университет<country>Россия</country></aff><aff xml:lang="en">N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences;&#13;
Novosibirsk State University<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Новосибирский национальный исследовательский государственный университет;&#13;
Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Novosibirsk State University;&#13;
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Новосибирский национальный исследовательский государственный университет<country>Россия</country></aff><aff xml:lang="en">Novosibirsk State University<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru">Новосибирский научно-исследовательский институт травматологии и ортопедии им. Я.Л. Цивьяна Министерства здравоохранения Российской Федерации<country>Россия</country></aff><aff xml:lang="en">Novosibirsk Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian Federation<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru">Новосибирский национальный исследовательский государственный университет;&#13;
Научно-исследовательский институт клинической и экспериментальной лимфологии – филиал Федерального исследовательского центра Институт цитологии и генетики Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Novosibirsk State University;&#13;
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-6"><aff xml:lang="ru">Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук;&#13;
Федеральный исследовательский центр Институт катализа им. Г.К. Борескова Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences;&#13;
Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-7"><aff xml:lang="ru">Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук;&#13;
Новосибирский национальный исследовательский государственный университет;&#13;
Федеральный исследовательский центр Институт катализа им. Г.К. Борескова Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences;&#13;
Novosibirsk State University;&#13;
Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-8"><aff xml:lang="ru">Новосибирский национальный исследовательский государственный университет;&#13;
Федеральный исследовательский центр Институт катализа им. Г.К. Борескова Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Novosibirsk State University;&#13;
Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-9"><aff xml:lang="ru">Федеральный исследовательский центр «Иркутский институт химии им. А.Е. Фаворского Сибирского отделения Российской академии наук»<country>Россия</country></aff><aff xml:lang="en">A.E. Favorsky Irkutsk Institute of Chemistry of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-10"><aff xml:lang="ru">Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-11"><aff xml:lang="ru">Новосибирский национальный исследовательский государственный университет;&#13;
Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук;&#13;
Курчатовский геномный центр ИЦиГ СО РАН<country>Россия</country></aff><aff xml:lang="en">Novosibirsk State University;&#13;
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences;&#13;
Kurchatov Genomic Center of ICG SB RAS<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>25</day><month>01</month><year>2025</year></pub-date><volume>28</volume><issue>8</issue><fpage>882</fpage><lpage>896</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Басов Н.В., Адамовская А.В., Рогачев А.Д., Гайслер Е.В., Деменков П.С., Иванисенко Т.В., Вензель А.С., Мишинов С.В., Ступак В.В., Чересиз С.В., Олешко О.С., Бутикова Е.А., Осечкова А.Е., Сотникова Ю.С., Патрушев Ю.В., Поздняков А.С., Лаврик И.Н., Иванисенко В.А., Покровский А.Г., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Басов Н.В., Адамовская А.В., Рогачев А.Д., Гайслер Е.В., Деменков П.С., Иванисенко Т.В., Вензель А.С., Мишинов С.В., Ступак В.В., Чересиз С.В., Олешко О.С., Бутикова Е.А., Осечкова А.Е., Сотникова Ю.С., Патрушев Ю.В., Поздняков А.С., Лаврик И.Н., Иванисенко В.А., Покровский А.Г.</copyright-holder><copyright-holder xml:lang="en">Basov N.V., Adamovskaya A.V., Rogachev A.D., Gaisler E.V., Demenkov P.S., Ivanisenko T.V., Venzel A.S., Mishinov S.V., Stupak V.V., Cheresiz S.V., Oleshko O.S., Butikova E.A., Osechkova A.E., Sotnikova Y.S., Patrushev Y.V., Pozdnyakov A.S., Lavrik I.N., Ivanisenko V.A., Pokrovsky A.G.</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/4410">https://vavilov.elpub.ru/jour/article/view/4410</self-uri><abstract><p>В ходе исследования проведен комплексный анализ метаболомных профилей глиобластомы и прилегающей ткани головного мозга, включавший 17 образцов глиобластомы и 15 образцов перитумо­ральной ткани. С использованием метода ВЭЖХ-МС/МС было проанализировано более 400 метаболитов, что позволило выявить значимые различия в их содержании между опухолевой и перитуморальной тканями. Статистический анализ, включавший тесты Манна–Уитни и Куккони, показал, что существенное количество метаболитов, в частности церамиды, значимо различается в тканях глиобластомы и перитуморального про­странства. Анализ метаболических путей из базы данных KEGG, выполненный с помощью MetaboAnalyst 6.0, выявил статистически значимую перепредставленность метаболизма сфинголипидов, что указывает на важ­ную роль этих липидных молекул в патогенезе глиобластомы. С использованием методов компьютерной системной биологии и искусственного интеллекта, реализованных в когнитивной системе ANDSystem, ре­конструированы молекулярно-генетические регуляторные пути, описывающие потенциальные механизмы нарушения функции ферментов метаболизма сфинголипидов. Реконструированные пути были объединены в регуляторную генную сеть. Данная сеть включала 15 генов, 329 белков и 389 взаимодействий, при этом 119 из 294 белков, регулирующих ключевые ферменты сфинголипидного метаболизма, оказались ассоции­рованы с глиобластомой. Анализ перепредставленности биологических процессов Gene Ontology показал статистическую значимость 184 процессов, в том числе апоптоза, сигнального пути NF-κB, пролиферации, миграции, ангиогенеза и пироптоза, многие из которых играют важную роль в онкогенезе. Результаты иссле­дования подчеркивают ключевую роль метаболизма сфинголипидов в развитии глиобластомы и открывают новые перспективы для разработки терапевтических подходов, направленных на его модуляцию.</p></abstract><trans-abstract xml:lang="en"><p>The metabolomic profiles of glioblastoma and surrounding brain tissue, comprising 17 glioblastoma samples and 15 peritumoral tissue samples, were thoroughly analyzed in this investigation. The LC-MS/MS method was used to analyze over 400 metabolites, revealing significant variations in metabolite content between tumor and peritumoral tissues. Statistical analyses, including the Mann–Whitney and Cucconi tests, identified several metabolites, particularly ceramides, that showed significant differences between glioblastoma and peritumoral tissues. Pathway analysis using the KEGG database, conducted with MetaboAnalyst 6.0, revealed a statistically sig­nificant overrepresentation of sphingolipid metabolism, suggesting a critical role of these lipid molecules in glio­blastoma pathogenesis. Using computational systems biology and artificial intelligence methods implemented in a cognitive platform, ANDSystem, molecular genetic regulatory pathways were reconstructed to describe potential mechanisms underlying the dysfunction of sphingolipid metabolism enzymes. These reconstructed pathways were integrated into a regulatory gene network comprising 15 genes, 329 proteins, and 389 interactions. Notably, 119 out of the 294 proteins regulating the key enzymes of sphingolipid metabolism were associated with glioblastoma. Analysis of the overrepresentation of Gene Ontology biological processes revealed the statistical significance of 184 processes, including apoptosis, the NF-kB signaling pathway, proliferation, migration, angiogenesis, and py­roptosis, many of which play an important role in oncogenesis. The findings of this study emphasize the pivotal role of sphingolipid metabolism in glioblastoma development and open new prospects for therapeutic approaches modulating this metabolism.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>глиобластома</kwd><kwd>перитуморальная ткань</kwd><kwd>маркеры</kwd><kwd>метаболомика</kwd><kwd>ВЭЖХ-МС/МС</kwd><kwd>сфинголи¬пиды</kwd><kwd>метаболические пути</kwd><kwd>генные сети</kwd><kwd>когнитивная система ANDSystem</kwd></kwd-group><kwd-group xml:lang="en"><kwd>glioblastoma</kwd><kwd>peritumoral tissue</kwd><kwd>markers</kwd><kwd>metabolomics</kwd><kwd>LC-MS/MS</kwd><kwd>sphingolipids</kwd><kwd>metabolic pathways</kwd><kwd>gene networks</kwd><kwd>cognitive system ANDSystem</kwd></kwd-group><funding-group xml:lang="en"><funding-statement>The production of monolithic columns for LC was made possible by the financial support of the FWUR-2024-0032 project. 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