KnowYourCG: Facilitating base-level sparse methylome interpretation.

Area of Science:

• Epigenetics and Genomics
• Computational Biology

Background:

• DNA methylomes are critical for understanding biological processes.
• Existing tools often focus on genes or intervals, limiting base-level analysis.
• Data sparsity in various methylation datasets poses challenges.

Purpose of the Study:

• To introduce KnowYourCG (KYCG), a novel data interpretation framework for functional DNA methylation analysis.
• To enable direct base-level screening of diverse biological and technical influences on DNA methylation.
• To address data sparsity issues in low-pass, single-cell, 5-hydroxymethylation, spatial, and array-based DNA methylation datasets.

Main Methods:

• KYCG implements efficient infrastructure for rapid screening of thousands of knowledgebases.
• It analyzes base-level influences including sequence motifs, transcription factor binding, histone modifications, replication timing, cell-type-specific methylation, and trait associations.
• The framework integrates seamlessly with standard assay technologies.

Main Results:

• KYCG provides valuable insights into cell differentiation and cancer origins.
• It aids in understanding epigenome-trait associations.
• The tool identifies and helps resolve technical issues like array artifacts, single-cell batch effects, and Nanopore 5-hydroxymethylation detection accuracy.

Conclusions:

• KYCG simplifies large-scale DNA methylation analysis.
• It offers a powerful approach for functional interpretation of diverse methylome data.
• The framework enhances biological insights from epigenetics research.