Деконволюционная оценка соотношения быстрых и медленных транскриптомных профилей и клеточного состава скелетных мышц человека по данным CAGE-seq

Представлен вычислительный метод для оценки клеточного состава образцов скелетной мышцы человека по данным CAGE-seq с использованием деконволюции. Подход позволяет оценить относительный вклад профилей экспресии, ассоциированных с быстрым и медленным фенотипами, без гистологической классификации. Входными данными служили транскриптомные профили CAGE, позволяющие точно определить уровень экспрессии и точку инициации транскрипции в промоторе. Для определения пропорций клеточных компонентов применяли метод деконволюции MuSiC с использованием данных секвенирования отдельных ядер мышц из проекта Heart Cell Atlas. На основе полученных оценок определен порог бинарного разделения по доле быстрых мышечных волокон (10%), показавший устойчивые характеристики (AUC = 0,934 и 0,828 для двух схем аннотации). Дальнейший анализ показал, что состав волокон и связанные с ним профили экспрессии отличаются между различными анатомическими группами мышц. Эти различия легли в основу функциональной аннотации, выявившей обогащение по биологическим процессам, связанным с развитием, специализацией мышечной ткани и возможными ассоциациями с патологией. Метод обеспечивает количественную, автоматизированную и воспроизводимую оценку спектра скоростных фенотипов скелетных мышц, открывая путь к стандартизации транскриптомного профилирования в фундаментальных и прикладных задачах.

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