Cellular Heterogeneity-Adjusted cLonal Methylation (CHALM) improves prediction of gene expression.

Cellular Heterogeneity-Adjusted cLonal Methylation (CHALM) improves prediction of gene expression.
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DOI:
10.1038/s41467-020-20492-7
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发表时间:
2021-01-15
影响因子:
16.6
通讯作者:
Li W
Li W
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xu J;Shi J;Cui X;Cui Y;Li JJ;Goel A;Chen X;Issa JP;Su J;Li W

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启动子 DNA 甲基化是一种成熟的转录抑制机制,尽管其与基因表达的整体相关性较弱。这种弱相关性可归因于当前的甲基化定量方法未能考虑测序的大细胞之间的异质性。在这里,我们引入细胞异质性调整克隆甲基化(CHALM)作为甲基化定量方法。 CHALM 增进了对 DNA 甲基化功能后果的理解,包括其与基因表达和 H3K4me3 的相关性。当应用于不同的甲基化数据集时,CHALM 方法能够检测差异甲基化基因,这些基因表现出支持潜在机制的不同生物学功能。在这里,作者介绍了细胞异质性调整克隆甲基化(CHALM)作为一种甲基化定量方法,考虑了已测序的大细胞的异质性。他们将 CHALM 应用于甲基化数据集,以检测差异甲基化基因,这些基因表现出支持潜在机制的不同生物学功能。
Promoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms. Here, the authors introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method that considers the heterogeneity of sequenced bulk cells. They apply CHALM to methylation datasets to detect differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.
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