KnowYourCG: Facilitating Base-Level Sparse Methylome Interpretation

KnowYourCG (KYCG) is a data interpretation framework 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 efficient infrastructure that rapidly screens thousands of knowledgebases, KYCG addresses data sparsity in low-pass or single-cell DNA methylomes, 5-hydroxymethylation (5hmC) profiles, spatial DNA methylation maps, and array-based datasets for EWAS.

Citation

Goldberg DC, Fu H, Atkins D, Moyer E, Lee CN, Deng Y, Zhou W. KnowYourCG: Facilitating base-level sparse methylome interpretation. Science Advances 11(43): eadw3027 (2025). https://doi.org/10.1126/sciadv.adw3027

Install knowYourCG

Release version can be installed from Bioconductor

BiocManager::install("knowYourCG")

Development version can be installed from github.

BiocManager::install('zhou-lab/knowYourCG')

Main Functions

Enrichment Testing

• testEnrichment - Test for enrichment of query in knowledgebase sets
• testEnrichment2 - Test enrichment from YAME-compressed CG sets
• testEnrichmentSEA - GSEA-like test for association of categorical variable against continuous variable
• testProbeProximity - Test if query probes share closer genomic proximity than random
• aggregateTestEnrichments - Aggregate test enrichment results

Database Management

• getDBs - Get databases by full or partial names
• listDBGroups - List database group names
• loadDBs - Load knowledgebase databases from TSV files
• buildGeneDBs - Build gene-probe association database
• dbStats - Aggregate methylation over database set features
• annoProbes - Annotate Probe IDs using KYCG databases

Visualization

• KYCG_plotBar - Bar plot of most enriched CG groups
• KYCG_plotDot - Dot plot of most enriched CG groups
• KYCG_plotEnrichAll - Plot enrichment test results
• KYCG_plotLollipop - Lollipop plot of log(estimate)
• KYCG_plotManhattan - Manhattan plot for EWAS results
• KYCG_plotMeta - Plot meta gene or other meta genomic features
• KYCG_plotMetaEnrichment - Plot meta gene enrichment
• KYCG_plotPointRange - Point range plot for enrichment results
• KYCG_plotSetEnrichment - Plot set enrichment
• KYCG_plotVolcano - Volcano plot of -log2(p.value) vs log(estimate)
• KYCG_plotWaterfall - Waterfall plot of log(estimate)

Data Access

• kycgDataCache - Cache KnowYourCG data
• kycgDataGet - Get KnowYourCG data

Utilities

• linkProbesToProximalGenes - Find genes in genomic proximity to Infinium probes
• bedToCg - Convert BED CpG set to YAME .cg format

See also

• YAME — sequence-level enrichment analysis (C command-line tool)
• Web application — interactive online queries
• Bioconductor release
• Bioconductor devel