Cellular heterogeneity–adjusted clonal methylation (CHALM) provides better prediction of gene expression

Jianfeng Xu, Jiejun Shi, Xiaodong Cui, Ya Cui, Jingyi Jessica Li, Ajay Goel, Xi Chen, Jianzhong Su, Jean-Pierre Issa, Wei Li

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Received Date: 19th February 20

Promoter DNA methylation is a well-established mechanism of transcription repression, but its global correlation with gene expression is surprisingly weak. This weak correlation is due in part 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 novel methylation quantification method. CHALM better explains the functional consequences of DNA methylation, such as its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method has uniquely detected differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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