Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66681610.31857/S0016675823080088XTNLERОБЗОРНЫЕ И ТЕОРЕТИЧЕСКИЕ СТАТЬИMethods for ChIP-seq Normalization and Their Application for Analysis of Regulatory Elements in Brain CellsМетоды нормализации данных ChIP-seq и их применение в исследованиях регуляторных участков генома клеток мозгаGusevF. E.ГусевФ. Е.gusev@vigg.ruAndreevaT. V.АндрееваТ. В.an_tati@vigg.ruRogaevE. I.РогаевЕ. И.evivrog@gmail.comVavilov Institute of General Genetics Russian Academy of SciencesИнститут общей генетики им. Н.И. Вавилова Российской академии наукCenter for Genetics and Life Science, “Sirius” University of Science and TechnologyНаучный центр генетики и науки о жизни, Университет “Сириус”0108202359885986926022025Copyright ©; 2023, Ф.Е. Гусев, Т.В. Андреева, Е.И. РогаевCopyright ©; 2023, Ф.Е. Гусев, Т.В. Андреева, Е.И. Рогаев2023Ф.Е. Гусев, Т.В. Андреева, Е.И. РогаевФ.Е. Гусев, Т.В. Андреева, Е.И. Рогаевhttps://transsyst.ru/0016-6758/article/view/666816

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has become one of the major tools to elucidate gene expression programs. Similar to other molecular profiling methods, ChIP-seq is sensetive to several technical biases which affect downstream results, especially in cases when material quality is difficult to control, for example, frozen post-mortem human tissue. However methods for bioinformatics analysis improve every year and allow to mitigate these effects after sequencing by adjusting for both technical ChIP-seq biases and more general biological biases like post-mortem interval or cell heterogenity of the sample. Here we review a wide selection of ChIP-seq normalization methods with a focus on application in specific experimental settings, in particular when brain tissue is investigated.

За последние годы метод иммунопреципитации хроматина с последующим глубоким секвенированием (ChIP-seq) стал одним из основных инструментов для исследования регуляции экспрессии генов. Как и другие способы молекулярного профилирования, ChIP-seq имеет ряд методических особенностей, которые могут оказывать нежелательный эффект на получаемые результаты, особенно в случаях, когда используются образцы клеток и тканей, качество которых сложно контролировать, например замороженные постмортальные образцы тканей мозга человека. Однако методы биоинформатического анализа совершенствуются с каждым годом и позволяют уменьшить эти эффекты на этапе анализа полученных данных секвенирования и позволяют сделать поправки (нормализовать данные) на неравномерность как технических особенностей ChIP-seq, так и в более общем смысле различных факторов исследований, например постмортальный интервал или гетерогенность клеточного состава исследуемых образцов. В этом обзоре мы рассмотрели широкий спектр предложенных методов нормализации данных ChIP-seq, особенности их применения и выбора в конкретном исследовании, в том числе в экспериментах с образцами клеток мозга человека. Представлены преимущества и недостатки существующих подходов к нормализации, а также примеры, свидетельствующие о перспективности использования методов ChIP-seq при исследовании мозга.

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