<?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">pharmjournal</journal-id><journal-title-group><journal-title xml:lang="ru">Разработка и регистрация лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Drug development &amp; registration</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2305-2066</issn><issn pub-type="epub">2658-5049</issn><publisher><publisher-name>LLC «CPHA»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33380/2305-2066-2025-14-3-2115</article-id><article-id custom-type="elpub" pub-id-type="custom">pharmjournal-2157</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>ДОКЛИНИЧЕСКИЕ И КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PRECLINICAL AND CLINICAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Автоматизированный количественный анализ окраса шерстного и кожного покрова лабораторных животных</article-title><trans-title-group xml:lang="en"><trans-title>Automated quantitative analysis of coat and skin coloration in laboratory animals</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4690-1811</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Приходько</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Prikhodko</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А</p></bio><bio xml:lang="en"><p>14A, Professora Popova str., Saint-Petersburg, 197022</p></bio><email xlink:type="simple">vaprikhodko@rambler.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/0000-0002-8214-7553</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ногаева</surname><given-names>У. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Nogaeva</surname><given-names>U. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А</p></bio><bio xml:lang="en"><p>14A, Professora Popova str., Saint-Petersburg, 197022</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/0000-0001-9273-6864</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ивкин</surname><given-names>Д. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivkin</surname><given-names>D. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А</p></bio><bio xml:lang="en"><p>14A, Professora Popova str., Saint-Petersburg, 197022</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/0000-0003-4294-5531</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Оковитый</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Okovityi</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, литера А</p></bio><bio xml:lang="en"><p>14A, Professora Popova str., Saint-Petersburg, 197022</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России)</institution></aff><aff xml:lang="en"><institution>Saint-Petersburg State Chemical and Pharmaceutical University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>02</day><month>09</month><year>2025</year></pub-date><volume>14</volume><issue>3</issue><fpage>178</fpage><lpage>187</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Приходько В.А., Ногаева У.В., Ивкин Д.Ю., Оковитый С.В., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Приходько В.А., Ногаева У.В., Ивкин Д.Ю., Оковитый С.В.</copyright-holder><copyright-holder xml:lang="en">Prikhodko V.A., Nogaeva U.V., Ivkin D.Y., Okovityi S.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.pharmjournal.ru/jour/article/view/2157">https://www.pharmjournal.ru/jour/article/view/2157</self-uri><abstract><sec><title>Введение</title><p>Введение. Анализ окраса шерстного и кожного покрова животных может использоваться как вспомогательный неинвазивный инструмент оценки ряда состояний и процессов, сопровождающихся изменением его цветности, насыщенности, долевого соотношения цветов шерсти или участков шерсти, подшерстка и кожи. Для проведения анализа окраса в условиях доклинических исследований требуется разработка простых, быстрых и легко стандартизуемых цифровых методов, обеспечивающих получение воспроизводимых результатов, пригодных для статистической обработки.</p></sec><sec><title>Цель</title><p>Цель. Целью настоящей работы стали разработка и апробация алгоритма количественного анализа окраса шерстного и кожного покрова лабораторных животных с использованием языка программирования R.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Для анализа шерстного покрова использовали цифровые фотоснимки самок морской свинки двух- и трехцветного окраса, сделанные в условиях искусственного освещения на однотонном контрастном фоне. Анализ соотношения участков шерсти и кожи выполняли с повторным использованием фотоснимков самца мыши с депиляционной моделью алопеции, сделанных в рамках ранее опубликованного доклинического исследования. Колориметрический анализ изображений осуществляли путем иерархической кластеризации цветов методом k-средних в пространстве RGB с расчетом площади кластеров с помощью пакета функций recolorize v0.2.0 для R v4.2.3 с RStudio v2025.05.0.</p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. Алгоритм колориметрического анализа включил три стадии: 1) преаналитическая обработка изображения и маскирование фона; 2) иерархическая кластеризация и рекластеризация цветов; 3) измерение абсолютных и относительных площадей цветовых кластеров. Посредством применения описанного алгоритма долевое соотношение цветов в окрасе двухцветной морской свинки было определено как 46,1 % агути и 53,9 % желтого; трехцветной – как 9,1 % рыжего, 19,6 % белого и 71,3 % черного. Для самца мыши после депиляции была охарактеризована динамика долевого соотношения участков кожи без волос и с растущими волосами в течение 28-дневного периода. Между 0-м, 9-м и 17-м днями после депиляции наблюдали сокращение относительной площади лишенной шерсти кожи от 8,7 до 7,4 и до 0,0 % соответственно (p &lt; 0,05 для 17-го дня против 0-го и 9-го).</p></sec><sec><title>Заключение</title><p>Заключение. В ходе проведенной работы описан и апробирован на модельных фотоснимках алгоритм количественного анализа окраса шерстного и кожного покрова с применением метода иерархической кластеризации цветов. Описанный алгоритм не требует использования специализированного программного обеспечения, быстр и прост в применении, подходит для серийной обработки изображений с получением количественных данных для дальнейшего статистического анализа.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Analysis of animal coat and skin coloration can be used as an auxiliary method for assessment of various conditions and processes that are accompanied by changes in coloration, intensity, proportion of coat colors or areas covered by fur, undercoat, and skin. Performing coloration analysis in preclinical studies requires new straightforward, fast, and easily standardizable digital methods that yield reproducible data suitable for statistical processing.</p></sec><sec><title>Aim</title><p>Aim. In this work, we aimed to develop and test a novel algorithm for quantitative analysis of coat and skin coloration in laboratory animals using R programming language.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. To analyse fur coloration, we used digital photographs of female guinea pigs, one bicolor and one calico, that were taken under artificial lighting against a plain contrasting background. Analysis of fur and skin area proportion was carried out re-using photographs of a male mouse with depilation alopecia model, which were obtained during a previously published preclinical study. Colorimetric image analysis was performed by hierarchical k-means color clustering in RGB space and cluster area calculation using the recolorize v0.2.0 function package for R v4.2.3 with RStudio v2025.05.0.</p></sec><sec><title>Results and discussion</title><p>Results and discussion. The algorithm for colorimetric analysis included 3 steps: 1) preprocessing images and masking the background; 2) hierarchical color clustering and reclustering; 3) calculating absolute and relative color cluster areas. Using the described algorithm, we found the color area proportion to be 46.1 % agouti vs. 53.9 % yellow for the bicolor guinea pig, and 9.1 % red vs. 19.6 % white vs. 71.3 % black, for the calico one. In the male mouse subjected to depilation, we characterized the dynamics of proportion between areas of hairless skin and skin with regrown hair across a 28 day-long period. We found a decrease in relative of hairless skin area between the 0th, 9th, and 17th days post-depilation from 8.7 to 7.4 % and to 0.0 %, respectively (p &lt; 0.05 for 17th day vs. 0th and 9th).</p></sec><sec><title>Сonclusion</title><p>Сonclusion. In this work, we described and tested on model photographs an algorithm for analysis of coat and skin coloration using hierarchical color clustering. The algorithm does not require the use of specialized software, is fast and straightforward, and can be employed for batch image processing to obtain quantitative data for further statistical analysis.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>анализ окраса</kwd><kwd>колориметрия</kwd><kwd>шерстный покров</kwd><kwd>кожный покров</kwd><kwd>алопеция</kwd><kwd>лабораторные животные</kwd></kwd-group><kwd-group xml:lang="en"><kwd>coloration analysis</kwd><kwd>colorimetry</kwd><kwd>coat</kwd><kwd>skin</kwd><kwd>alopecia</kwd><kwd>laboratory animals</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Результаты работы получены с использованием оборудования ЦКП «Аналитический центр ФГБОУ ВО СПХФУ Минздрава России» в рамках соглашения № 075-2021-685 от 26 июля 2021 года при финансовой поддержке Минобрнауки России.</funding-statement><funding-statement xml:lang="en">The results of this work were obtained using the equipment of the Center for Collective Use "Analytical Center of the Saint-Petersburg Chemical Pharmaceutical University" (agreement No. 075-15-2021-685 from 26 July 2021) with financial  support from the Ministry of Science and Higher Education of the Russian Federation.</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">Caro T., Mallarino R. Coloration in Mammals. Trends in Ecology and Evolution. 2020;35(4):357–366. DOI: 10.1016/j.tree.2019.12.008.</mixed-citation><mixed-citation xml:lang="en">Caro T., Mallarino R. Coloration in Mammals. Trends in Ecology and Evolution. 2020;35(4):357–366. DOI: 10.1016/j.tree.2019.12.008.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Rochin L., Hurbain I., Serneels L., Fort C., Watt B., Leblanc P., Marks M. S., De Strooper B., Raposo G., van Niel G. BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells. Proceedings of the National Academy of Sciences. 2013;110(26):10658–10663. DOI: 10.1073/pnas.1220748110.</mixed-citation><mixed-citation xml:lang="en">Rochin L., Hurbain I., Serneels L., Fort C., Watt B., Leblanc P., Marks M. S., De Strooper B., Raposo G., van Niel G. BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells. Proceedings of the National Academy of Sciences. 2013;110(26):10658–10663. DOI: 10.1073/pnas.1220748110.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Tharmarajah G., Faas L., Reiss K., Saftig P., Young A., Van Raamsdonk C. D. Adam10 haploinsufficiency causes freckle-like macules in Hairless mice. Pigment Cell and Melanoma Research. 2012;25(5):555–565. DOI: 10.1111/j.1755-148X.2012.01032.x.</mixed-citation><mixed-citation xml:lang="en">Tharmarajah G., Faas L., Reiss K., Saftig P., Young A., Van Raamsdonk C. D. Adam10 haploinsufficiency causes freckle-like macules in Hairless mice. Pigment Cell and Melanoma Research. 2012;25(5):555–565. DOI: 10.1111/j.1755-148X.2012.01032.x.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Papalazarou V., Swaminathan K., Jaber-Hijazi F., Spence H., Lahmann I., Nixon C., Salmeron-Sanchez M., Arnold H.-H., Rottner K., Machesky L. M. The Arp2/3 complex is critical for colonisation of the mouse skin by melanoblasts. Development. 2020;147(22):dev194555. DOI: 10.1242/dev.194555.</mixed-citation><mixed-citation xml:lang="en">Papalazarou V., Swaminathan K., Jaber-Hijazi F., Spence H., Lahmann I., Nixon C., Salmeron-Sanchez M., Arnold H.-H., Rottner K., Machesky L. M. The Arp2/3 complex is critical for colonisation of the mouse skin by melanoblasts. Development. 2020;147(22):dev194555. DOI: 10.1242/dev.194555.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Fan R., Gao J. Establishment of a promising vitiligo mouse model for pathogenesis and treatment studies. Diagnostic Pathology. 2024;19(1):92. DOI: 10.1186/s13000-024-01520-2.</mixed-citation><mixed-citation xml:lang="en">Fan R., Gao J. Establishment of a promising vitiligo mouse model for pathogenesis and treatment studies. Diagnostic Pathology. 2024;19(1):92. DOI: 10.1186/s13000-024-01520-2.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lenartowicz M., Krzeptowski W., Lipiński P., Grzmil P., Starzyński R., Pierzchała O., Møller L. B. Mottled Mice and Non-Mammalian Models of Menkes Disease. Frontiers in Molecular Neuroscience. 2015;8:72. DOI: 10.3389/fnmol.2015.00072.</mixed-citation><mixed-citation xml:lang="en">Lenartowicz M., Krzeptowski W., Lipiński P., Grzmil P., Starzyński R., Pierzchała O., Møller L. B. Mottled Mice and Non-Mammalian Models of Menkes Disease. Frontiers in Molecular Neuroscience. 2015;8:72. DOI: 10.3389/fnmol.2015.00072.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Sundberg J. P., Wang E. H. C., McElwee K. J. Current Protocols: Alopecia Areata Mouse Models for Drug Efficacy and Mechanism Studies. Current Protocols. 2024;4(8):e1113. DOI: 10.1002/cpz1.1113.</mixed-citation><mixed-citation xml:lang="en">Sundberg J. P., Wang E. H. C., McElwee K. J. Current Protocols: Alopecia Areata Mouse Models for Drug Efficacy and Mechanism Studies. Current Protocols. 2024;4(8):e1113. DOI: 10.1002/cpz1.1113.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Shipkowski K. A., Hubbard T. D., Ryan K., Waidyanatha S., Cunny H., Shockley K. R., Allen J. L., Toy H., Levine K., Harrington J., Betz L., Sparrow B., Roberts G. K. Shortterm toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice. Toxicology Reports. 2023;10:621–632. DOI: 10.1016/j.toxrep.2023.05.003.</mixed-citation><mixed-citation xml:lang="en">Shipkowski K. A., Hubbard T. D., Ryan K., Waidyanatha S., Cunny H., Shockley K. R., Allen J. L., Toy H., Levine K., Harrington J., Betz L., Sparrow B., Roberts G. K. Shortterm toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice. Toxicology Reports. 2023;10:621–632. DOI: 10.1016/j.toxrep.2023.05.003.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Chen C. C., Murray P. J., Jiang T. X., Plikus M. V., Chang Y. T., Lee O. K., Widelitz R. B., Chuong C. M. Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4. The Journal of Investigative dermatology. 2014;134(8):2086–2096. DOI: 10.1038/jid.2014.139.</mixed-citation><mixed-citation xml:lang="en">Chen C. C., Murray P. J., Jiang T. X., Plikus M. V., Chang Y. T., Lee O. K., Widelitz R. B., Chuong C. M. Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4. The Journal of Investigative dermatology. 2014;134(8):2086–2096. DOI: 10.1038/jid.2014.139.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Kreienkamp R., Gonzalo S. Metabolic Dysfunction in Hutchinson-Gilford Progeria Syndrome. Cells. 2020;9(2):395. DOI: 10.3390/cells9020395.</mixed-citation><mixed-citation xml:lang="en">Kreienkamp R., Gonzalo S. Metabolic Dysfunction in Hutchinson-Gilford Progeria Syndrome. Cells. 2020;9(2):395. DOI: 10.3390/cells9020395.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Sakamoto M., Nakano T., Tsuge I., Yamanaka H., Katayama Y., Shimizu Y., Note Y., Inoie M., Morimoto N. Dried human cultured epidermis accelerates wound healing in diabetic mouse skin defect wounds. Scientific Reports. 2022;12(1):3184. DOI: 10.1038/s41598-022-07156-w.</mixed-citation><mixed-citation xml:lang="en">Sakamoto M., Nakano T., Tsuge I., Yamanaka H., Katayama Y., Shimizu Y., Note Y., Inoie M., Morimoto N. Dried human cultured epidermis accelerates wound healing in diabetic mouse skin defect wounds. Scientific Reports. 2022;12(1):3184. DOI: 10.1038/s41598-022-07156-w.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Rahul V. G., Ellur G., Gaber A. A., Govindappa P. K., Elfar J. C. 4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice. Cell Death Discovery. 2024;10(1):428. DOI: 10.1038/s41420-024-02199-6.</mixed-citation><mixed-citation xml:lang="en">Rahul V. G., Ellur G., Gaber A. A., Govindappa P. K., Elfar J. C. 4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice. Cell Death Discovery. 2024;10(1):428. DOI: 10.1038/s41420-024-02199-6</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Семивеличенко Е. Д., Ермолаева А. А., Пономаренко В. В., Новоселов А. В., Плиско Г. А., Ивкин Д. Ю., Антонов В. Г., Карев В. Е., Титович И. А., Ерёмин А. В. Исследование эффективности действия препаратов на основе молекулярных комплексов аденозин-полимер на модели термического ожога. Разработка и регистрация лекарственных средств. 2022;11(3):209–219. DOI: 10.33380/2305-2066-2022-11-3-209-219.</mixed-citation><mixed-citation xml:lang="en">Semivelichenko E. D., Ermolaeva A. A., Ponomarenko V. V., Novoselov A. V., Plisko G. A., Ivkin D. Yu., Antonov V. G., Karev V. E., Titovich I. A., Eremin A. V. Study of the Effectiveness of Drugs Based on Molecular Complexes of Adenosine-polymer on the Model of Thermal Burn. Drug development &amp; registration. 2022;11(3):209–219. (In Russ.) DOI: 10.33380/2305-2066-2022-11-3-209-219.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Voisey J., van Daal A. Agouti: from mouse to man, from skin to fat. Pigment Cell Research. 2002;15(1):10–18. DOI: 10.1034/j.1600-0749.2002.00039.x.</mixed-citation><mixed-citation xml:lang="en">Voisey J., van Daal A. Agouti: from mouse to man, from skin to fat. Pigment Cell Research. 2002;15(1):10–18. DOI: 10.1034/j.1600-0749.2002.00039.x.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Cropley J. E., Suter C. M., Beckman K. B., Martin D. I. K. Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(46):17308–17312. DOI: 10.1073/pnas.0607090103.</mixed-citation><mixed-citation xml:lang="en">Cropley J. E., Suter C. M., Beckman K. B., Martin D. I. K. Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(46):17308–17312. DOI: 10.1073/pnas.0607090103.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Ounpraseuth S., Rafferty T. M., McDonald-Phillips R. E., Gammill W. M., Siegel E. R., Wheeler K. L., Nilsson E. A., Cooney C. A. A method to quantify mouse coat-color proportions. PLoS ONE. 2009;4(4):e5414. DOI: 10.1371/journal.pone.0005414.</mixed-citation><mixed-citation xml:lang="en">Ounpraseuth S., Rafferty T. M., McDonald-Phillips R. E., Gammill W. M., Siegel E. R., Wheeler K. L., Nilsson E. A., Cooney C. A. A method to quantify mouse coat-color proportions. PLoS ONE. 2009;4(4):e5414. DOI: 10.1371/journal.pone.0005414.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Lavado A., Olivares C., García-Borrón J. C., Montoliu L. Molecular basis of the extreme dilution mottled mouse mutation: a combination of coding and noncoding genomic alterations. The Journal of Biological Chemistry. 2005;280(6):4817–4824. DOI: 10.1074/jbc.M410399200.</mixed-citation><mixed-citation xml:lang="en">Lavado A., Olivares C., García-Borrón J. C., Montoliu L. Molecular basis of the extreme dilution mottled mouse mutation: a combination of coding and noncoding genomic alterations. The Journal of Biological Chemistry. 2005;280(6):4817–4824. DOI: 10.1074/jbc.M410399200.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Weller H. I., Hiller A. E., Lord N. P., Van Belleghem S. M. recolorize: An R package for flexible colour segmentation of biological images. Ecology Letters. 2024;27(2):e14378. DOI: 10.1111/ele.14378.</mixed-citation><mixed-citation xml:lang="en">Weller H. I., Hiller A. E., Lord N. P., Van Belleghem S. M. recolorize: An R package for flexible colour segmentation of biological images. Ecology Letters. 2024;27(2):e14378. DOI: 10.1111/ele.14378.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Ногаева У. В., Ивкин Д. Ю., Плиско Г. А., Флисюк Е. В., Ковансков В. Е., Штырлин Ю. Г., Сидоров К. О. Сравнительная эффективность трансдермальных форм для терапии алопеции. Разработка и регистрация лекарственных средств. 2021;10(4):171–178. DOI: 10.33380/2305-2066-2021-10-4(1)-171-178.</mixed-citation><mixed-citation xml:lang="en">Nogaeva U. V., Ivkin D. Yu., Plisko G. A., Flisyuk E. V., Kovanskov V. E., Shtyrlin Yu. G., Sidorov K. O. Comparative efficacy of transdermal forms for alopecia therapy. Drug Development &amp; Registration. 2021;10(4):171–178. (In Russ.) DOI: 10.33380/2305-2066-2021-10-4(1)-171-178.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Wickham H., Averick M., Bryan J., Chang W., McGowan L. D., François R., Grolemund G., Hayes A., Henry L., Hester J., Kuhn M., Pedersen T. L., Miller E., Bache S. M., Müller K., Ooms J., Robinson D., Seidel D. P., Spinu V., Takahashi K., Vaughan D., Wilke C., Woo K., Yutani H. Welcome to the tidyverse. Journal of Open Source Software. 2019;4(43):1686. DOI: 10.21105/joss.01686.</mixed-citation><mixed-citation xml:lang="en">Wickham H., Averick M., Bryan J., Chang W., McGowan L. D., François R., Grolemund G., Hayes A., Henry L., Hester J., Kuhn M., Pedersen T. L., Miller E., Bache S. M., Müller K., Ooms J., Robinson D., Seidel D. P., Spinu V., Takahashi K., Vaughan D., Wilke C., Woo K., Yutani H. Welcome to the tidyverse. Journal of Open Source Software. 2019;4(43):1686. DOI: 10.21105/joss.01686.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Badano A., Revie C., Casertano A., Cheng W. C., Green P., Kimpe T., Krupinski E., Sisson C., Skrøvseth S., Treanor D., Boynton P., Clunie D., Flynn M. J., Heki T., Hewitt S., Homma H., Masia A., Matsui T., Nagy B., Nishibori M., Penczek J., Schopf T., Yagi Y., Yokoi H, Summit on Color in Medical Imaging. Consistency and standardization of color in medical imaging: a consensus report. Journal of Digital Imaging. 2015;28(1):41–52. DOI: 10.1007/s10278-014-9721-0.</mixed-citation><mixed-citation xml:lang="en">Badano A., Revie C., Casertano A., Cheng W. C., Green P., Kimpe T., Krupinski E., Sisson C., Skrøvseth S., Treanor D., Boynton P., Clunie D., Flynn M. J., Heki T., Hewitt S., Homma H., Masia A., Matsui T., Nagy B., Nishibori M., Penczek J., Schopf T., Yagi Y., Yokoi H, Summit on Color in Medical Imaging. Consistency and standardization of color in medical imaging: a consensus report. Journal of Digital Imaging. 2015;28(1):41–52. DOI: 10.1007/s10278-014-9721-0.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Савельев Д. С., Городков С. Ю., Горемыкин И. В. Стандартизация колориметрии медицинской фотографии в клинической практике. Детская хирургия. 2024;28(5):460– 471. DOI: 10.17816/ps803.</mixed-citation><mixed-citation xml:lang="en">Savelyev D. S., Gorodkov S. Y., Goremykin I. V. Standardization of color measurement in the medical photography in clinical practice. Russian Journal of Pediatric Surgery. 2024;28(5):460–471. (In Russ.) DOI: 10.17816/ps803.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Bonetto A., Andersson D. C., Waning D. L. Assessment of muscle mass and strength in mice. BoneKEy Reports. 2015;4:732. DOI: 10.1038/bonekey.2015.101.</mixed-citation><mixed-citation xml:lang="en">Bonetto A., Andersson D. C., Waning D. L. Assessment of muscle mass and strength in mice. BoneKEy Reports. 2015;4:732. DOI: 10.1038/bonekey.2015.101.</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>
