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Disease diagnosis using cell-free DNA (cfDNA) has been an active research field recently. Most existing approaches perform diagnosis based on the detection of sequence variants on cfDNA; thus, their applications are limited to diseases associated with high mutation rate such as cancer. Recent developments start to exploit the epigenetic information on cfDNA, which could have substantially wider applications. In this work, we provide thorough reviews and discussions on the statistical method developments and data analysis strategies for using cfDNA epigenetic profiles, in particular DNA methylation, to construct disease diagnostic models. We focus on two important aspects: marker selection and prediction model construction, under different scenarios. We perform simulations and real data analysis to compare different approaches, and provide recommendations for data analysis.

Disease prediction by cell-free DNA methylation