<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">medgen</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская генетика</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Genetics</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2073-7998</issn><publisher><publisher-name>Publishing House «Genius Media» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.25557/2073-7998.2025.10.135-138</article-id><article-id custom-type="elpub" pub-id-type="custom">medgen-3265</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>КРАТКОЕ СООБЩЕНИЕ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BRIEF REPORT</subject></subj-group></article-categories><title-group><article-title>Оригинальный подход к выявлению геномных локусов, ассоциированных с полигенными заболеваниями, основанный на использовании методов случайного леса и ресемплинга</article-title><trans-title-group xml:lang="en"><trans-title>An Original Approach to Identifying Genomic Loci Associated with Polygenic Diseases Based on Random Forest and Resampling</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>Хворых</surname><given-names>Г. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Khvorykh</surname><given-names>G. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>123182, Москва, пл. Академика Курчатова, д. 2</p></bio><bio xml:lang="en"><p>2, Akademika Kurchatova sq., Moscow, 123182 </p></bio><email xlink:type="simple">gennady.khvorykh@gmail.com</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>Сапожников</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Sapozhnikov</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>123182, Москва, пл. Академика Курчатова, д. 2</p></bio><bio xml:lang="en"><p>2, Akademika Kurchatova sq., Moscow, 123182 </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>Лимборская</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Limborska</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>123182, Москва, пл. Академика Курчатова, д. 2</p><p>115522, Москва, ул. Москворечье, д. 1 </p></bio><bio xml:lang="en"><p>2, Akademika Kurchatova sq., Moscow, 123182 </p><p>1, Moskvorechye st, Moscow,115522 </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>Хрунин</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Khrunin</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>123182, Москва, пл. Академика Курчатова, д. 2</p></bio><bio xml:lang="en"><p>2, Akademika Kurchatova sq., Moscow, 123182 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ Национальный исследовательский центр «Курчатовский институт»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Research Centre «Kurchatov Institute»</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБУ Национальный исследовательский центр «Курчатовский институт» ; ФГБНУ Медико-генетический научный центр имени академика Н.П. Бочкова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Research Centre «Kurchatov Institute» ; Research Centre for Medical Genetics</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>24</day><month>11</month><year>2025</year></pub-date><volume>24</volume><issue>10</issue><fpage>135</fpage><lpage>138</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Хворых Г.В., Сапожников Н.А., Лимборская С.А., Хрунин А.В., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Хворых Г.В., Сапожников Н.А., Лимборская С.А., Хрунин А.В.</copyright-holder><copyright-holder xml:lang="en">Khvorykh G.V., Sapozhnikov N.A., Limborska S.A., Khrunin A.V.</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://www.medgen-journal.ru/jour/article/view/3265">https://www.medgen-journal.ru/jour/article/view/3265</self-uri><abstract><p>Для выявления геномных локусов, связанных с полигенными заболеваниями, альтернативой традиционным полногеномным ассоциативным исследованиям является машинное обучение с ранжированием признаков по важности вклада в прогнозную модель. Чтобы это реализовать, нужно решить проблему дисбаланса классов, обусловленную разницей размеров выборок больных и контроля, и научиться отбирать признаки по важности вклада − метрике, которая в отличие от p-значений, не имеет порога. В работе представлен биоинформатический подход, решающий обе задачи одновременно. Он основан на обучении алгоритма случайного леса на рандомизированных выборках больных и контроля схожего размера с ранжированием признаков по уменьшению важности вклада и отбором по частоте встречаемости среди топовых значений, а также стабильности важности вклада. Подход апробирован на симулированных генотип-фенотипических данных, содержащих однонуклеотидные полиморфизмы. Использовали два набора искусственных данных. В одном случае они включали локусы, ассоциированные с полигенным заболеванием, а в другом такие локусы не назначались.</p></abstract><trans-abstract xml:lang="en"><p>For the detection of genomic loci associated with polygenic diseases, an alternative to traditional genome-wide association studies is machine learning with feature ranking according to importance contribution to predictive model performance. To implement this approach, it is necessary to address the class imbalance problem caused by differences in the size of case and control samples, and learn how to select features based on their importance metric, which unlike p-values does not have a threshold. This work presents a bioinformatic approach that solves both problems simultaneously. It is based on training a random forest algorithm on randomized case-control samples of similar size, followed by feature ranking according to decreasing importance score and selection based on frequency among top-ranked values, as well as stability of importance scores. The approach has been tested on simulated genotypephenotype data containing single nucleotide polymorphisms. Two types of synthetic datasets were applied. The first one contained the genomic loci associated with polygenic disease. The second one did not have such loci.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>полногеномное ассоциативное исследование</kwd><kwd>машинное обучение</kwd><kwd>полигенное заболевание</kwd><kwd>однонуклеотидный полиморфизм</kwd></kwd-group><kwd-group xml:lang="en"><kwd>genome-wide association study</kwd><kwd>polygenic disease</kwd><kwd>machine learning</kwd><kwd>single nucleotide polymorphism</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при финансовой поддержке гранта РНФ № 23-14-00131.</funding-statement><funding-statement xml:lang="en">This research was supported by the Russian Science Foundation, grant number 23-14-00131.</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">Khvorykh G., Belousov M., Limborska S. et al. The performance of machine learning approach in genome-wide association study of disease. The Proceedings of 14th International Conference on Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/ SB-2024), Novosibirsk, Russia, August 5-10, 2024:846-848. doi: 10.18699/bgrs2024-4.3-08</mixed-citation><mixed-citation xml:lang="en">Khvorykh G., Belousov M., Limborska S. et al. The performance of machine learning approach in genome-wide association study of disease. The Proceedings of 14th International Conference on Bioinformatics of Genome Regulation and Structure/Systems Biology (BGRS/ SB-2024), Novosibirsk, Russia, August 5-10, 2024:846-848. doi: 10.18699/bgrs2024-4.3-08</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Nikolić S., Ignatov D.I., Khvorykh G.V. et al. Genome-wide association studies of ischemic stroke based on interpretable machine learning. PeerJ Computer Science. 2024;10:e2454. doi: 10.7717/peerj-cs.2454</mixed-citation><mixed-citation xml:lang="en">Nikolić S., Ignatov D.I., Khvorykh G.V. et al. Genome-wide association studies of ischemic stroke based on interpretable machine learning. PeerJ Computer Science. 2024;10:e2454. doi: 10.7717/peerj-cs.2454</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Purcell S., Neale B., Todd-Brown K. et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet. 2007;81(3):559-75. doi: 10.1086/519795</mixed-citation><mixed-citation xml:lang="en">Purcell S., Neale B., Todd-Brown K. et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet. 2007;81(3):559-75. doi: 10.1086/519795</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Bonett D.G., Seier E. Confidence Interval for a Coefficient of Dispersion in Nonnormal Distributions. Biometrical Journal. 2006;48(1):144-148. doi: 10.1002/bimj.200410148</mixed-citation><mixed-citation xml:lang="en">Bonett D.G., Seier E. Confidence Interval for a Coefficient of Dispersion in Nonnormal Distributions. Biometrical Journal. 2006;48(1):144-148. doi: 10.1002/bimj.200410148</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>
