DNA Methylation Imputation Across Platforms.

In this chapter, we will provide a review on imputation in the context of DNA methylation, specifically focusing on a penalized functional regression (PFR) method we have previously developed. We will start with a brief review of DNA methylation, genomic and epigenomic contexts where imputation has proven beneficial in practice, and statistical or computational methods proposed for DNA methylation in the recent literature (Subheading 1). The rest of the chapter (Subheadings 2-4) will provide a detailed review of our PFR method proposed for across-platform imputation, which incorporates nonlocal information using a penalized functional regression framework. Subheading 2 introduces commonly employed technologies for DNA methylation measurement and describes the real dataset we have used in the development of our method: the acute myeloid leukemia (AML) dataset from The Cancer Genome Atlas (TCGA) project. Subheading 3 comprehensively reviews our method, encompassing data harmonization prior to model building, the actual building of penalized functional regression model, post-imputation quality filter, and imputation quality assessment. Subheading 4 shows the performance of our method in both simulation and the TCGA AML dataset, demonstrating that our penalized functional regression model is a valuable across-platform imputation tool for DNA methylation data, particularly because of its ability to boost statistical power for subsequent epigenome-wide association study. Finally, Subheading 5 provides future perspectives on imputation for DNA methylation data.