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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/VJ21.035</article-id><article-id custom-type="elpub" pub-id-type="custom">vavilov-3015</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 И КОМПЬЮТЕРНАЯ БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>SYSTEMS AND COMPUTATIONAL BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Технологии поиска и исследования потенциально осциллирующих ферментативных систем</article-title><trans-title-group xml:lang="en"><trans-title>The finding and researching algorithm for potentially oscillating enzymatic systems</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1729-7712</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лахова</surname><given-names>Т. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Lakhova</surname><given-names>T. N.</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">tlakhova@bionet.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/0000-0002-5711-7539</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Казанцев</surname><given-names>Ф. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kazantsev</surname><given-names>F. 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/0000-0003-3138-381X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лашин</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Lashin</surname><given-names>S. 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-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7754-8611</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Матушкин</surname><given-names>Ю. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Matushkin</surname><given-names>Yu. 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">Курчатовский геномный центр ИЦиГ СО РАН<country>Россия</country></aff><aff xml:lang="en">Kurchatov Genomics Center of ICG SB RAS<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Курчатовский геномный центр ИЦиГ СО РАН;&#13;
Новосибирский национальный исследовательский государственный университет<country>Россия</country></aff><aff xml:lang="en">Kurchatov Genomics Center of ICG SB RAS;&#13;
Novosibirsk State University<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук;&#13;
Новосибирский национальный исследовательский государственный университет<country>Россия</country></aff><aff xml:lang="en">Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences;&#13;
Novosibirsk State University<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>02</day><month>06</month><year>2021</year></pub-date><volume>25</volume><issue>3</issue><fpage>318</fpage><lpage>330</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Лахова Т.Н., Казанцев Ф.В., Лашин С.А., Матушкин Ю.Г., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Лахова Т.Н., Казанцев Ф.В., Лашин С.А., Матушкин Ю.Г.</copyright-holder><copyright-holder xml:lang="en">Lakhova T.N., Kazantsev F.V., Lashin S.A., Matushkin Y.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/3015">https://vavilov.elpub.ru/jour/article/view/3015</self-uri><abstract><p>Многие процессы в живых организмах подвержены периодическим колебаниям на различных иерархических уровнях их организации: от молекулярного-генетического до популяционного и экологического. Осциллирующие процессы отвечают за клеточные циклы как у прокариот, так и у эукариот, за циркадные ритмы, синхронную связь дыхания с сердечными сокращениями и др. Колебания численностей организмов в природных популяциях могут быть обусловлены собственными свойствами популяций, их возрастной структурой, а также экологическими взаимоотношениями с другими видами. Наряду с экспериментальными подходами, для исследования осциллирующих биологических систем широко применяется математическое и компьютерное моделирование. В данной статье представлены классические математические модели, которые описывают осциллирующее поведение в биологических системах. Приведены методы поиска осциллирующих молекулярно-генетических систем на примере их частного случая – осциллирующих ферментативных систем. Рассмотрены факторы, влияющие на циклическую динамику в живых системах, характерные не только для молекулярно-генетического уровня, но и для более высоких уровней организации. Обсуждается применение различных способов описания генных сетей для моделирования осциллирующих молекулярно-генетических систем, где важнейшим фактором возникновения циклического поведения является наличие обратных связей. Представлены технологии поиска потенциально осциллирующих ферментативных систем. С помощью метода, описанного в статье, проводится поэтапный процесс построения и анализа сначала структурных моделей (графов) генных сетей, а затем реконструкции математических моделей и вычислительных экспериментов с ними. Структурные модели идеально подходят для задач автоматического поиска потенциальных осциллирующих контуров (связных подграфов), структура которых может соответствовать математической модели молекулярно-генетической системы, демонстрирующей осциллирующее поведение в динамике. При этом именно численное исследование математических моделей для отобранных контуров позволяет подтвердить наличие в них устойчивых предельных циклов. В качестве примера применения технологии проанализирована сеть из 300 метаболических реакций бактерии Escherichia coli с использованием инструментов математического и компьютерного моделирования. В частности, показано осциллирующее поведение для контура, реакции которого входят в путь биосинтеза триптофана.</p></abstract><trans-abstract xml:lang="en"><p>Many processes in living organisms are subject to periodic oscillations at different hierarchical levels of their organization: from molecular-genetic to population and ecological. Oscillatory processes are responsible for cell cycles in both prokaryotes and eukaryotes, for circadian rhythms, for synchronous coupling of respiration with cardiac contractions, etc. Fluctuations in the numbers of organisms in natural populations can be caused by the populations’ own properties, their age structure, and ecological relationships with other species. Along with experimental approaches, mathematical and computer modeling is widely used to study oscillating biological systems. This paper presents classical mathematical models that describe oscillatory behavior in biological systems. Methods for the search for oscillatory molecular-genetic systems are presented by the example of their special case – oscillatory enzymatic systems. Factors influencing the cyclic dynamics in living systems, typical not only of the molecular-genetic level, but of higher levels of organization as well, are considered. Application of different ways to describe gene networks for modeling oscillatory molecular-genetic systems is considered, where the most important factor for the emergence of cyclic behavior is the presence of feedback. Techniques for finding potentially oscillatory enzymatic systems are presented. Using the method described in the article, we present and analyze, in a step-by-step manner, first the structural models (graphs) of gene networks and then the reconstruction of the mathematical models and computational experiments with them. Structural models are ideally suited for the tasks of an automatic search for potential oscillating contours (linked subgraphs), whose structure can correspond to the mathematical model of the molecular-genetic system that demonstrates oscillatory behavior in dynamics. At the same time, it is the numerical study of mathematical models for the selected contours that makes it possible to confirm the presence of stable limit cycles in them. As an example of application of the technology, a network of 300 metabolic reactions of the bacterium Escherichia coli was analyzed using mathematical and computer modeling tools. In particular, oscillatory behavior was shown for a loop whose reactions are part of the tryptophan biosynthesis pathway.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>осцилляции</kwd><kwd>обратная связь</kwd><kwd>циклические процессы</kwd><kwd>моделирование биологических систем</kwd></kwd-group><kwd-group xml:lang="en"><kwd>oscillations</kwd><kwd>feedback</kwd><kwd>cyclic processes</kwd><kwd>modelling of biological systems</kwd></kwd-group><funding-group xml:lang="en"><funding-statement>This work was supported by the Budget Project No. 0259-2021-0009 “Systems biology and bioinformatics: reconstruction, analysis and modeling of the structural and functional organization and evolution of gene networks of humans, animals, plants and microorganisms” and the Russian Science Foundation project No. 18-14-00293 (visualization and structural analysis of graphs of metabolic networks)</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">Akinshin A.A., Golubyatnikov V.P. 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