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CLASSIFYING SUBJECTS BASED ON THEIR BIOLOGICAL RESPONSE TO UV IRRADIATION

机译:根据其对紫外线辐射的生物反应进行分类主题

摘要

The present invention relates to methods for classifying humans into Molecular Phototypes based on the biological response of their skin to UV irradiation. The method comprises: a) providing skin cells irradiated with UV light obtained from a plurality of human subjects; b) determining the methylation levels and/or expression levels of at least about 100 features in said skin cells, wherein the features are selected from CpG sites and RNAs; c) using the methylation data and/or expression data obtained in step b) to generate a subject similarity network; d) performing cluster analysis on the subject similarity network; and e) defining Molecular Phototypes based on the clusters in the subject similarity network. The invention also relates to methods for identifying biological pathways that are associated with the response to UV irradiation of skin in human subjects belonging to a Molecular Phototype determined by a method described herein. The method comprises: a) providing skin cells irradiated with UV light and control skin cells obtained from a plurality of human subjects belonging to a Molecular Phototype determined by a method described herein; b) determining the expression levels of at least one gene in said irradiated and control skin cells, wherein the at least one gene is annotated to a biological pathway; c) using a machine-learning model trained on the data obtained in step b) to identify whether said at least one gene can discriminate between irradiated and control skin cells; and d) determining the strength of the association between the biological pathway and the response to UV irradiation of skin in the human subjects belonging to the Molecular Phototype, wherein the strength of the association is based on the degree to which the machine-learning model can discriminate between irradiated and control skin cells. Also provided are computer programs relating to the methods.
机译:本发明涉及将人类分解成分子光拷贝的方法,基于皮肤皮肤对紫外线辐射。该方法包括:a)提供用从多个人受试者获得的UV光照射的皮肤细胞; b)在所述皮肤细胞中测定至少约100个特征的甲基化水平和/或表达水平,其中所述特征选自CPG位点和RNA; c)使用在步骤b)中获得的甲基化数据和/或表达数据来生成主体相似性网络; d)对主题相似性网络进行集群分析;并且e)基于主体相似性网络中的簇定义分子光学型。本发明还涉及用于鉴定与属于通过本文所述方法确定的分子光型的人受试者对皮肤抗紫外线照射相关的生物途径的方法。该方法包括:a)提供用紫外​​光照射的皮肤细胞,并控制由属于本文所述方法测定的分子光学的多个人受试者获得的皮肤细胞; b)确定所述辐照和对照皮肤细胞中至少一种基因的表达水平,其中所述至少一种基因被注释为生物途径; c)使用在步骤b中获得的数据培训的机器学习模型,以识别所述至少一个基因是否可以区分辐照和对照皮肤细胞; D)确定生物途径与属于分子光学的人受试者的皮肤响应的关系的强度,其中关联的强度基于机器学习模型可以的程度区分辐照和控制皮肤细胞。还提供了与方法相关的计算机程序。

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