Cell type deconvolution of methylated cell-free DNA at the resolution of individual reads

• DOI: 10.1093/nargab/lqad048
• Publication Date: 2023-06-02T21:18:42Z
• Authors: Pia Keukeleire; Stavros Makrodimi...; Marcel Reinders
• Keywords: CpG site; Cell type; Cell-free fetal DNA; Differentially methylated regions

Cell-free DNA (cfDNA) are fragments originating from dying cells that detectable in bodily fluids, such as the plasma. Accelerated cell death, for example caused by disease, induces an elevated concentration of cfDNA. As a result, determining type origins cfDNA molecules can provide information about individual's health. In this work, we aim to increase sensitivity methylation-based deconvolution adapting existing method, CelFiE, which uses methylation beta values individual CpG sites estimate proportions. Our new CelFEER, instead differentiates types average within reads. We additionally improved originally reported performance CelFiE using approach finding marker regions differentially methylated between types. show CelFEER estimates proportions with higher correlation (r = 0.94 ± 0.04) than 0.86 0.09) on simulated mixtures Moreover, proportion estimated differentiate ALS patients and healthy controls, pregnant women their first third trimester, without gestational diabetes.