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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">inform</journal-id><journal-title-group><journal-title xml:lang="ru">Информатика</journal-title><trans-title-group xml:lang="en"><trans-title>Informatics</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1816-0301</issn><issn pub-type="epub">2617-6963</issn><publisher><publisher-name>UIIP NASB</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.37661/1816-0301-2025-22-3-45-58</article-id><article-id custom-type="elpub" pub-id-type="custom">inform-1364</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</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOINFORMATICS</subject></subj-group></article-categories><title-group><article-title>Алгоритм выбора референсных микроРНК при классификации биологических процессов</article-title><trans-title-group xml:lang="en"><trans-title>Algorithm for selecting reference microRNAs in biological processes classification</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4150-282X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Красько</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Krasko</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Красько Ольга Владимировна - кандидат технических наук, доцент, ведущий научный сотрудник.</p><p>ул. Сурганова, 6, Минск, 220012</p></bio><bio xml:lang="en"><p>Olga V. Krasko - Ph. D. (Eng.), Assoc. Prof., Leading Researcher, The United Institute of Informatics Problems of the National Academy of Sciences of Belarus.</p><p>Surganova st., 6, Minsk, 220012</p></bio><email xlink:type="simple">krasko@newman.bas-net.by</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3759-7050</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Якубовский</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Yakubouski</surname><given-names>S. U.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Якубовский Сергей Владимирович - кандидат медицинских наук, доцент, доцент кафедры хирургии и трансплантологии с курсом повышения квалификации и переподготовки.</p><p>пр. Дзержинского, 83, Минск, 220083</p></bio><bio xml:lang="en"><p>Siarhei U. Yakubouski - Ph. D. (Med.), Assoc. Prof., Assoc. Prof. of Department of Surgery and Transplantology with Advanced Training and Retraining Courses, Belarusian State Medical University.</p><p>Dzerzhinski av., 83, Minsk, 220116</p></bio><email xlink:type="simple">yakub-2003@yandex.by</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7822-0746</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кипень</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Kipen</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кипень Вячеслав Николаевич - кандидат биологических наук, доцент, ведущий научный сотрудник.</p><p>ул. Академическая, 27, Минск, 220072</p></bio><bio xml:lang="en"><p>Viachaslau N. Kipen - Ph. D. (Biol.), Assoc. Prof., Leading Researcher, The Institute of Genetics and Cytology of the National Academy of Sciences of Belarus.</p><p>Akademicheskaya st., 27, Minsk, 220072</p></bio><email xlink:type="simple">v.kipen@igc.by</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Объединенный институт проблем информатики Национальной академии наук Беларуси</institution></aff><aff xml:lang="en"><institution>The United Institute of Informatics Problems of the National Academy of Sciences of Belarus</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Белорусский государственный медицинский университет</institution></aff><aff xml:lang="en"><institution>Belarusian State Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Институт генетики и цитологии Национальной академии наук Беларуси</institution></aff><aff xml:lang="en"><institution>The Institute of Genetics and Cytology of the National Academy of Sciences of Belarus</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>10</day><month>10</month><year>2025</year></pub-date><volume>22</volume><issue>3</issue><fpage>45</fpage><lpage>58</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Красько О.В., Якубовский С.В., Кипень В.Н., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Красько О.В., Якубовский С.В., Кипень В.Н.</copyright-holder><copyright-holder xml:lang="en">Krasko O.V., Yakubouski S.U., Kipen V.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" 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://inf.grid.by/jour/article/view/1364">https://inf.grid.by/jour/article/view/1364</self-uri><abstract><sec><title>Ц е л и</title><p>Ц е л и. Целью исследования является разработка алгоритма выбора референсных микроРНК с учетом их взаимосвязи с тем, чтобы классифицировать группы образцов при изучении различных биологических процессов.</p></sec><sec><title>М е т о д ы</title><p>М е т о д ы. Использовались методы линейной алгебры, анализа главных компонент, статистических моделей бинарной регрессии, оценки производительности моделей.</p></sec><sec><title>Р е з у л ь т а т ы</title><p>Р е з у л ь т а т ы. Разработан новый алгоритм MDSeek, который предлагает выбор референсных микроРНК для нормализации данных количественной полимеразной цепной реакции с целью последующего использования нормализованных данных для задач классификации. Оценка результатов работы алгоритма для задачи классификации свидетельствует о его более высокой эффективности по сравнению с известными подходами к нормализации результатов полимеразной цепной реакции.</p></sec><sec><title>З а к л ю ч е н и е</title><p>З а к л ю ч е н и е. В настоящей работе предложен оригинальный алгоритм MDSeek, предназначенный для выбора референсных микроРНК с целью нормализации результатов полимеразной цепной реакции и позволяющий изучать изменения экспрессии микроРНК при сравнении различных биологических процессов. После применения MDSeek на опытном наборе образцов нормализованные данные использовались для задач классификации, метрики производительности были лучше по сравнению с другими алгоритмами.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>O b j e c t i v e s</title><p>O b j e c t i v e s. The algorithm for selection of reference microRNA taking into account their biological features for classification of pathologies.</p><p>Development of an algorithm for selecting microRNAs with regard to their interconnection for samples classification in the various biological processes.</p></sec><sec><title>M e t h o d s</title><p>M e t h o d s. Methods of linear algebra, principal component analysis, statistical binary regression models, and model performance metrics were used.</p></sec><sec><title>R e s u l t s</title><p>R e s u l t s. A new algorithm, MDSeek, has been developed that proposes a selection of reference microRNA for the normalization quantitative polymerase chain reaction results taking into account their coexpression. MDSeek demonstrates higher performance metrics compared to known reference gene selection approaches for the subsequent classification tasks.</p></sec><sec><title>C o n c l u s i o n</title><p>C o n c l u s i o n. An original MDSeek algorithm for selecting reference microRNAs for normalization results of polymerase chain reaction is suggested. It takes into account changes in microRNA expression when comparing different biological processes. After applying MDSeek to an experimental set of samples, the normalized data were used for classification tasks, and the performance metrics were better than those of other normalization algorithms.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>микроРНК</kwd><kwd>нормализация</kwd><kwd>полимеразная цепная реакция</kwd><kwd>классификация</kwd><kwd>расстояние Махаланобиса</kwd><kwd>производительность моделей</kwd></kwd-group><kwd-group xml:lang="en"><kwd>MicroRNA</kwd><kwd>normalization</kwd><kwd>polymerase chain reaction</kwd><kwd>classification</kwd><kwd>Mahalanobis distance</kwd><kwd>model performance</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Vandesompele J., De Preter K., Pattyn F., Poppe B., Van Roy N., …, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology, 2002, vol. 3, рр. 1–12.</mixed-citation><mixed-citation xml:lang="en">Vandesompele J., De Preter K., Pattyn F., Poppe B., Van Roy N., …, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology, 2002, vol. 3, рр. 1–12.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Karlen Y., McNair A., Perseguers S., Mazza C., Mermod N. Statistical significance of quantitative PCR. BMC Bioinformatics, 2007, vol. 8, рр. 1–16.</mixed-citation><mixed-citation xml:lang="en">Karlen Y., McNair A., Perseguers S., Mazza C., Mermod N. Statistical significance of quantitative PCR. BMC Bioinformatics, 2007, vol. 8, рр. 1–16.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Maltseva D. V., Khaustova N. A., Fedotov N. N., Matveeva E. O., Lebedev A. E., …, Tonevitsky A. G. High-throughput identification of reference genes for research and clinical RT-qPCR analysis of breast cancer samples. Journal of Clinical Bioinformatics, 2013, vol. 3, рр. 1–12.</mixed-citation><mixed-citation xml:lang="en">Maltseva D. V., Khaustova N. A., Fedotov N. N., Matveeva E. O., Lebedev A. E., …, Tonevitsky A. G. High-throughput identification of reference genes for research and clinical RT-qPCR analysis of breast cancer samples. Journal of Clinical Bioinformatics, 2013, vol. 3, рр. 1–12.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Mar J. C., Kimura Y., Schroder K., Irvine K. M., Hayashizaki Y., …, Quackenbush J. Data-driven normalization strategies for high-throughput quantitative RT-PCR. BMC Bioinformatics, 2009, vol. 10, рр. 1–10.</mixed-citation><mixed-citation xml:lang="en">Mar J. C., Kimura Y., Schroder K., Irvine K. M., Hayashizaki Y., …, Quackenbush J. Data-driven normalization strategies for high-throughput quantitative RT-PCR. BMC Bioinformatics, 2009, vol. 10, рр. 1–10.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Bustin S. A., V. Benes, J. A Garson, J. Hellemans, J. Huggett, …, Wittwer C. T. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clinical Chemistry, 2009, vol. 55, no. 4, рр. 611–622.</mixed-citation><mixed-citation xml:lang="en">Bustin S. A., V. Benes, J. A Garson, J. Hellemans, J. Huggett, …, Wittwer C. T. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clinical Chemistry, 2009, vol. 55, no. 4, рр. 611–622.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Jacob F., Guertler R., Naim S., Nixdorf S., Fedier A., …, Heinzelmann-Schwarz V. Careful selection of reference genes is required for reliable performance of RT-qPCR in human normal and cancer cell lines. PloS One, 2013, vol. 8, no. 3, р. e59180.</mixed-citation><mixed-citation xml:lang="en">Jacob F., Guertler R., Naim S., Nixdorf S., Fedier A., …, Heinzelmann-Schwarz V. Careful selection of reference genes is required for reliable performance of RT-qPCR in human normal and cancer cell lines. PloS One, 2013, vol. 8, no. 3, р. e59180.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Pfaffl M. W., Tichopad A., Prgomet C., Neuvians T. P. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper – Excel-based tool using pair-wise correlations. Biotechnology Letters, 2004, vol. 26, рр. 509–515.</mixed-citation><mixed-citation xml:lang="en">Pfaffl M. W., Tichopad A., Prgomet C., Neuvians T. P. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper – Excel-based tool using pair-wise correlations. Biotechnology Letters, 2004, vol. 26, рр. 509–515.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Andersen C. L., Jensen J. L., Ørntoft T. F. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Research, 2004, vol. 64, no. 15, рр. 5245–5250.</mixed-citation><mixed-citation xml:lang="en">Andersen C. L., Jensen J. L., Ørntoft T. F. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Research, 2004, vol. 64, no. 15, рр. 5245–5250.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Grabia S., Smyczynska U., Pagacz K., Fendler W. NormiRazor: tool applying GPU-accelerated computing for determination of internal references in microRNA transcription studies. BMC Bioinformatics, 2020, vol. 21, рр. 1–16.</mixed-citation><mixed-citation xml:lang="en">Grabia S., Smyczynska U., Pagacz K., Fendler W. NormiRazor: tool applying GPU-accelerated computing for determination of internal references in microRNA transcription studies. BMC Bioinformatics, 2020, vol. 21, рр. 1–16.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Marabita F., de Candia P., Torri A., Tegnér J., Abrignani S., Rossi R. L. Normalization of circulating microRNA expression data obtained by quantitative real-time RT-PCR. Briefings in Bioinformatics, 2016, vol. 17, no. 2, рр. 204–212.</mixed-citation><mixed-citation xml:lang="en">Marabita F., de Candia P., Torri A., Tegnér J., Abrignani S., Rossi R. L. Normalization of circulating microRNA expression data obtained by quantitative real-time RT-PCR. Briefings in Bioinformatics, 2016, vol. 17, no. 2, рр. 204–212.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Friedman R. C., Farh K. K., Burge C. B., Bartel D. P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research, 2009, vol. 19, no. 1, рр. 92–105. DOI: 10.1101/gr.082701.108.</mixed-citation><mixed-citation xml:lang="en">Friedman R. C., Farh K. K., Burge C. B., Bartel D. P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research, 2009, vol. 19, no. 1, рр. 92–105. DOI: 10.1101/gr.082701.108.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Iorio M. V., Croce C. M. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Molecular Medicine, 2012, vol. 4, no. 3, рр. 143–159. DOI: 10.1002/emmm.201100209.</mixed-citation><mixed-citation xml:lang="en">Iorio M. V., Croce C. M. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Molecular Medicine, 2012, vol. 4, no. 3, рр. 143–159. DOI: 10.1002/emmm.201100209.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Boufraqech M., Klubo-Gwiezdzinska J., Kebebew E. MicroRNAs in the thyroid. Best Practice &amp; Research Clinical Endocrinology &amp; Metabolism, 2016, vol. 30, iss. 5, рр. 603–619. DOI: 10.1016/j.beem.2016.10.001.</mixed-citation><mixed-citation xml:lang="en">Boufraqech M., Klubo-Gwiezdzinska J., Kebebew E. MicroRNAs in the thyroid. Best Practice &amp; Research Clinical Endocrinology &amp; Metabolism, 2016, vol. 30, iss. 5, рр. 603–619. DOI: 10.1016/j.beem.2016.10.001.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Yoshida K., Yokoi A., Yamamoto Y., Kajiyama H. ChrXq27.3 miRNA cluster functions in cancer development. Journal of Experimental &amp; Clinical Cancer Research, 2021, vol. 40, iss. 1, р. 112. DOI: 10.1186/s13046-021-01910-0.</mixed-citation><mixed-citation xml:lang="en">Yoshida K., Yokoi A., Yamamoto Y., Kajiyama H. ChrXq27.3 miRNA cluster functions in cancer development. Journal of Experimental &amp; Clinical Cancer Research, 2021, vol. 40, iss. 1, р. 112. DOI: 10.1186/s13046-021-01910-0.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Mahalanobis, P. C. On the generalized distance in statistics. Proceedings of National Institute Science in India, 1936, vol. 2, рр. 49–55.</mixed-citation><mixed-citation xml:lang="en">Mahalanobis, P. C. On the generalized distance in statistics. Proceedings of National Institute Science in India, 1936, vol. 2, рр. 49–55.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">De Maesschalck R., Jouan-Rimbaud D., Massart D. L. The mahalanobis distance. Chemometrics and Intelligent Laboratory Systems, 2000, vol. 50, no. 1, рр. 1–18.</mixed-citation><mixed-citation xml:lang="en">De Maesschalck R., Jouan-Rimbaud D., Massart D. L. The mahalanobis distance. Chemometrics and Intelligent Laboratory Systems, 2000, vol. 50, no. 1, рр. 1–18.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Touloumis A. Nonparametric Stein-type shrinkage covariance matrix estimators in high-dimensional settings. Computational Statistics &amp; Data Analysis, 2015, vol. 83, рр. 251–261.</mixed-citation><mixed-citation xml:lang="en">Touloumis A. Nonparametric Stein-type shrinkage covariance matrix estimators in high-dimensional settings. Computational Statistics &amp; Data Analysis, 2015, vol. 83, рр. 251–261.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
