Abstract
DNA methylation plays crucial roles in many biological processes and abnormal DNA methylation patterns are often observed in diseases. Recent studies have shed light on cis-acting DNA elements that regulate locus-specific DNA methylation, which involves transcription factors, histone modification and DNA secondary structures. In addition, several recent studies have surveyed DNA motifs that regulate DNA methylation and suggest potential applications in diagnosis and prognosis. Here, we discuss the current biological foundation for the cis-acting genetic code that regulates DNA methylation. We review the computational models that predict DNA methylation with genetic features and discuss the biological insights revealed from these models. We also provide an in-depth discussion on how to leverage such knowledge in clinical applications, particularly in the context of liquid biopsy for early cancer diagnosis and treatment.