Abstract
DNA methylation (DNAm)-based cell mixture deconvolution (CMD) has become a quintessential part of epigenome-wide association studieswhere DNAm is profiled in heterogeneous tissue types. Despite being introduced over a decade ago, detection limits, which represent the smallest fraction of a cell type in a mixed biospecimen that can be reliably detected, have yet to be determined in the context of DNAm-based CMD. Moreover, there has been little attention given to approaches for quantifying the uncertainty associated with DNAm-based CMD. Here, analytical frameworks for determining both cell-specific limits of detection and quantification of uncertainty associated with DNAm-based CMD are described. This work may contribute to improved rigor, reproducibilityand replicability of epigenome-wide association studies involving CMD.
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