# KnowYourCG: Facilitating base-level sparse methylome interpretation

## TL;DR

KnowYourCG is a new tool that helps scientists interpret DNA methylation data at the base level, uncovering biological and technical insights.

## Contribution

KnowYourCG introduces a CpG-based framework for base-level methylome analysis, enabling insights into diverse biological and technical factors.

## Key findings

- KYCG enables base-level screening of methylation data for biological and technical influences.
- The tool effectively handles sparse methylation datasets like single-cell and low-pass methylomes.
- Applications of KYCG reveal insights into cancer origins, cell differentiation, and technical artifacts.

## Abstract

Decoding DNA methylomes for biological insights is critical in epigenetics research. We present KnowYourCG (KYCG), a data interpretation framework designed for functional DNA methylation analysis. Unlike existing tools that target genes or genomic intervals, KYCG features direct base-level screenings of diverse biological and technical influences, including sequence motifs, transcription factor binding, histone modifications, replication timing, cell-type–specific methylation, and trait associations. Through implementing efficient infrastructure that rapidly screens and investigates thousands of knowledgebases, KYCG addresses the challenges of data sparsity in various methylation datasets, including low-pass or single-cell DNA methylomes, 5-hydroxymethylation (5hmC) profiles, spatial DNA methylation maps, and array-based datasets for epigenome-wide association studies. Applying KYCG to these datasets provides valuable insights into cell differentiation, cancer origins, epigenome-trait associations, and technical issues such as array artifacts, single-cell batch effects, and Nanopore 5hmC detection accuracy. Our tool simplifies large-scale methylation analysis and integrates seamlessly with standard assay technologies.

KnowYourCG is a scalable, CpG-based framework for DNA methylome interpretation for broad biological and technical links.