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.

启动子DNA甲基化是一种公认​​的转录抑制机制，尽管其与基因表达的整体相关性较弱。这种弱的相关性可以归因于当前的甲基化量化方法未能考虑测序的大细胞之间的异质性。在这里，我们介绍细胞异质性调整后的甲基化甲基化（CHALM）作为甲基化量化方法。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。当将CHALM方法应用于不同的甲基化数据集时，它能够检测出差异甲基化的基因，这些基因表现出支持潜在机制的独特生物学功能。